Disclosed is a novel carbapenem derivative having a substituted imidazo5,1-bthiazole group at the 2-position on the carbapenem ring have high anti microbial activities against -lactamase producing bacteria, MRSA, resistant-Pseudomonas aeruginosa, PRSP, enterococci, and influenza, and high stabilities to DHP-1. According to the present invention, there is provided a compound represented by the formula (I), or a pharmacologically acceptable salt thereof or an ester at the 3-position on the carbapenem ring thereof:

Description

264 parts

›This is a continuation of Ser. No. 09/744,583…

This is a continuation of Ser. No. 09/744,583, filed Jan. 26, 2001, now U.S. Pat. No. 6,458,780 which is a 371 of PCT/JP99/04025, filed Jul. 27, 1999.

›BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to a carbapenem compound which has excellent antimicrobial activity and wide range of anti-microbial spectrum, and can be administered not only as an injection but also orally. More particularly, the present invention relates to a novel carbapenem derivative which has a substituted imidazo[5,1-b]thiazole group or a salt thereof.

2. Background Art

Carbapenem derivatives, by virtue of potent antibacterial activity against a wide spectrum of bacteria, have been energetically studied as a highly useful β-lactam agent, and Imipenem, Panipenem, and Meropenem have been clinically used.

Both Imipenem and Panipenem, however, are used as a mixture due to instability against renal dehydropeptidase-1 (“DHP-1”) in the case of Imipenem and in order to reduce nephrotoxicity in the case of Panipenem. Meropenem which has recently been marketed has a methyl group at the 1β-position, so that it has increased stability to DHP-1 and thus can be used alone.

However, a need still exists for a drug having higher stability to DHP-1. Furthermore, drugs effective for methicillin resistant Staphylococcus aureus (“MRSA”), penicillin resistant Streptococcus pneumoneae (“PRSP”), resistant Pseudomonas aeruginosa and enterococci which have recently become serious problems as well as influenza have been demanded as well.

Some of the present inventors have previously reported the carbapenem derivatives having a novel heteroaromatic ring imidazo[5,1-b]thiazolium-6-ylmethyl group at the 2-position on the carbapenem ring in WO 96/028455 and the carbapenem derivatives having an imidazo[5,1-b]thiazole group through a pyrrolidinylthio group at the 2-position of the carbapenem ring in W98/023623 and, furthermore, the carbapenem derivatives having an imidazo[5,1-b]thiazole group directly at the 2-position of the carbapenem ring in WO98/032760.

Further, WO96/011932 and WO96/034868 and Japanese Patent Laid-Open Publication No. 273876/1992 disclose the carbapenem derivatives in which a carbon atom on the heteroaromatic ring is bonded to the 2-position of the carbapenem ring. However, there have been described no specifictdata on the anti-microbial activities or effectiveness for these derivatives. There have been described neither bicyclic heteroaromatic rings nor carbapenem rings having imidazo[5,1-b]thiazole group.

›SUMMARY OF THE INVENTION

The present inventors have now found that novel carbapenem derivatives having a substituted imidazo[5,1-b]thiazole group at the 2-position on the carbapenem ring have high anti-microbial activities against β-lactamase producing bacteria, MRSA, resistant- Pseudomonas aeruginosa , PRSP, enterococci, and influenza, and high stabilities to DHP-1. The present invention is based on such findings.

Accordingly, the object of the present invention is to provide novel compounds which have wide range of anti-gram-positive and gram-negative microbial activities, especially high anti-microbial activities against microorganisms including β-lactamase producing bacteria, MRSA, enterococci, PRSP, influenza, and high stabilities to DHP-1.

According to the present invention, there is provided a compound represented by the formula (I), or a pharmacologically acceptable salt thereof or an ester at the 3-position on the carbapeem ring thereof:

wherein

R 1 represents a hydrogen atom or a methyl group,

R 2 , R 3 , R 4 , and R 5 , either one of which represents the bonding to the 2-position on the carbapenem ring, and the other three of which may be the same or different, respectively represent

a hydrogen atom,

a halogen atom,

a nitro group,

a cyano group,

a lower alkyl group which may be'substituted,

a lower cycloalkyl group which may be substituted,

a lower alkylthio group,

an arylthio group,

a C 2-4 alkenyl group which may be substituted,

a formyl group,

a lower alkylcarbonyl group which may be substituted,

a lower alkoxycarbonyl group,

a lower alkylsulfonyl group,

an arylsulfonyl group which may be substituted,

an aminosulfonyl group,

an N-loweralkylaminosulfonyl group which may be substituted,

an N,N-di-lower alkylaminosulfonyl group which may be substituted,

an N-lower alkoxy-N-lower alkylaminosulfonyl group,

a lowerialkylsufinyl group

an arylsulfinyl group,

an aminosulfinyl group,

an arylcarbonyl group,

an arylgroup which may be substituted,

a carbamoyl group,

an N-lower alkylcarbamoyl group,

an N,N-di-lower alkylaminocarbonyl group,

a lowerialkoxyiminomethyl group,

a hydroxyiminomethyl group, or

a five- or six-membered aromatic heterocyclic ring having one or more hetero atoms selected from nitrogen, oxygen and sulfur atoms, and

R represents a hydrogen atom or a group which may be hydrolyzed in organisms.

›DETAILED DESCRIPTION OF THE INVENTION · 1 of 17

Definition

As used herein, the term “lower alkyl” or “lower alkoxy” as a group or a part of a group means a straight chain or branched chain alkyl of alkyloxy having 1-6 carbon atoms, preferably 1-4 carbonatoms. Theexamples of the lower alkyl include methyl, ethyl, n-propyl, isopropyl, n-butyl, i-butyl, s-butyl, t-butyl, n-pentyl, n-hexyl, and the like. Further, the lower alkoxy includes by way of example methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, i-butoxy, s-butoxy, t-butoxy, and the like.

The term “lower cycloalkyl” means monocyclic alkyl having 3-6 carbon atoms.

Further, the term “aryl” means an aromatic ring and aromatic polycyclic hydrocabon ring preferably phenyl or naphthyl.

The term “halogen” herein means fluorine, chlorine, bromine, or iodine.

Compound

In the formula (I), any one of R 2 , R 3 , R 4 , and R 5 represents the bond to the 2-position on the carbapenem ring. The remaining three groups, which may be the same or different, respectively represent a hydrogen atom, a halogen atom, a nitro group, a cyano group, a lower alkyl group which may be substituted, a lower cycloalkyl group which may be substituted, a lower alkylthio group, an arylthio group, a C 2-4 alkenyl group which may be substituted, a formyl group, a lower alkylcarbonyl group which may be substituted, a lower alkoxycarbonyl group, a lower alkylsulfonyl group, an arylsulfonyl group which may be substituted, an aminosulfonyl group, an N-loweralkylaminosulfonyl group which may be substituted, an N,N-di-lower alkylaminosulfonyl group which may substituted, an N-lower alkoxy-N-lower alkylaminosulfonyl group, a lower alkylsufinyl group, an arylsulfinyl group, an aminosulfinyl group, an arylcarbonyl group, an aryl group which may be substituted, a carbamoyl group, an N-lower alkylcarbamoyl group, an N,N-di-lower alkylaminocarbonyl group, a lower alkoxyiminomethyl group, a hydroxyiminomethyl group, or a five- or six-membered aromatic heterocyclic ring having one or more hetero atoms selected from nitrogen, oxygen and sulfur atoms.

According to the preferred embodiment of the present invention, the remaining three groups, which may be the same or different, respectively represent a hydrogen atom, a halogen atom, a cyano group, a lower alkyl group which may be substituted, a lower cycloalkyl group which may be substituted, a lower alkylthio group, an arylthio group, a C 2-4 alkenyl group which may be substituted, a formyl group, a lower alkylcarbonyl group which may be substituted, a lower alkylsulfonyl group, an arylsulfonyl group which may be substituted, an aminosulfonyl group, an N-loweralkylaminosulfonyl group which may be substituted, an N,N-di-lower alkylaminosulfonyl group which may be substituted, a lower alkylsufinyl group, an arylcarbonyl group, an aryl group which be substituted, a lower alkoxyiminomethyl group, a hydroxyiminomethyl group, or a five- or six-membered aromatic heterocyclic ring having one or more hetero atoms selected from nitrogen, oxygen and sulfur atoms. More preferably, the remaining three groups represent a hydrogen atom, a halogen atom, a cyano group, a lower alkyl group (in which one or more hydrogen atoms on the alkyl group may be substituted by groups selected from the group consisting of a halogen atom, a hydroxy group, an amino group, a formylamino group, a lower alkylcarbonylamino group, acarbamoylgroup, andalower alkylsulfonylaminogroup), a lower cycloalkyl group which may be substituted by carbamoyl, a lower alkylthio group, an a rylthio group, a C 2-4 alkenyl group (in which one or more hydrogen atoms on the alkenyl group may be substituted by a lower alkylcarbonyl group or a lower alkoxycarbonyl group), a formyl group, a lower alkylcarbonyl group (in which one or more hydrogen atoms on the alkyl group may be substituted by groups selected from the group consisting of a halogen atom, a hydroxy group, an amino group, a lower alkylcarbonylamino group, N,N-di-lower alkylaminocarbonyl group, an (N-lower alkylamino)sulfonylamino group, an (N,N-di-lower alkylamino)sulfonylamino group and a lower alkylsulfonylamino group), a lower alkylsulfonyl group, anlarylsulfonyl group (in which one or more hydrogen atoms may beisubstituted by a lower alkyl group), an aminosulfonyl group, an N-loweralkylaminosulfonyl group (in which one or more hydrogen atoms on the alkyl group may be substituted by groups selected from the group consisting of a lower alkoxy group, a hydroxy group, and an aryl group (in which one or more hydrogen atoms on the aryl group may be substituted by an amino group)), an N,N-di-lower alkylaminosulfonyl group, a lower alkylsufinyl group, an arylcarbonyl group, an aryl group which be substituted by a lower alkylcarbonyl group, a lower alkoxyiminomethyl group, a hydroxyiminomethyl group, or a five- or six-membered aromatic heterocyclic ring having one or more hetero atoms (nitrogen, oxygen or sulfur atom).

In R 2 , R 3 , R 4 , R 5 and R which represent lower alkyl, one or more hydrogen atoms on the lower alkyl may be substituted by halogen, nitro, cyano, lower cycloalkyl, lower alkylthio, lower alkoxy, hydroxy, amino, N-lower alkylamino, formyl, lower alkylcarbonyl, arylcarbonyl, carboxy, lower alkoxycarbonyl, formylamino, lower alkylcarbonylamino, carbamoyl, N-lower alkylcarbamoyl, N,N-di-lower alkylaminocarbonyl, aminosulfonyl, (N-lower alkylamino)sulfonyl, (N,N-di-lower alkylamino)sulfonyl, (N-lower alkylamino)sulfonylamino, aminosulfonylamino, (N,N-di-lower alkylamino)sulfonylamino, lower alkylsulfonylamino, and aryl. According to the preferred embodiment of the present invention, the substituent includes preferably halogen, hydroxy, amino, formylamino, lower alkylcarbonyl, carbamoyl and lower alkylsulfonyamino. The substituted alkyl includes for example aminomethyl, hydroxymethyl, 2-hydroxyethyl, carbamoylmethyl, 2-carbamoylethyl, 2-fluoroethyl, cyclopropylmethyl, 2-(N-methylcarbamoyl)ethyl, N,N-dimethylcarbamoylmethyl, 2-(N,N-dimethylcarbamoyl)ethyl, 2-aminosulfonylaminoethyl, aminosulfonylaminomethyl, 2-(aminosulfonylamino)ethyl, methoxymethyl, ethoxycarbonylmethyl, formylaminomethyl, methoxyiminomethyl, hydroxyiminomethyl, and benzyl.

›DETAILED DESCRIPTION OF THE INVENTION · 2 of 17

In R 2 , R 3 , R 4 , and R 5 which represent lower cycloalkyl, one or more hydrogen atoms on the cycloalkyl may be substituted by a group selected from the group consisting of lower alkyl, halogen, nitro, cyano, lower alkylthio, lower alkoxy, hydroxy, amino, N-lower alkylamino, formyl, lower alkylcarbonyl, arylcarbonyl, carboxy, lower alkoxycarbonyl, formylamino, lower alkylcarbonylamino, carbamoyl, N-lower alkylcarbamoyl, N,N-di-lower alkylaminocarbonyl, aminosulfonyl, (N-lower alkylamino)sulfonyl, (N,N-di-lower alkylamino)sulfonyl, (N-lower alkylamino)sulfonylamino, aminosulfonylamino, (N,N-di-lower alkylamino)sulfonylarino, and aryl, more preferably carbamoyl.

Furthermore, in R 2 , R 3 , R 4 , and R 5 which represent alkenyl, one or more hydrogen atoms on the alkenyl may be substituted, and the substituent includes for example a group selected from the group consisting of lower alkyl, halogen, nitro, cyano, lower cycloalkyl, lower alkylthio, lower alkoxy, hydroxy, amino, N-lower alkylamino, formyl, lower alkylcarbonyl, arylcarbonyl, carboxyl, lower alkoxycarbonyl, formylamino, lower alkylcarbonylamino, carbamoyl, N-lower alkylcarbamoyl, N,N-di-lower alkylaminocarbonyl, aminosulfonyl, (N-lower alkylamino)sulfonyl, (N,N-di-lower alkylamino)sulfonyl, (N-lower alkylamino)sulfonylamino, aminosulfonylamino, (N,N-di-lower alkylamino)sulfonylamino, and aryl, more preferably lower alkylcarbonyl and lower alkoxycarbonyl.

In R 2 , R 3 , R 4 , and R 5 which represent lower alkylcarbonyl, one or more hydrogen atoms on the, group may be substituted, and the substituent includes for example a group selected from the group consisting of halogen, nitro, cyano, lower cycloalkyl, lower alkylthio, lower alkoxy, hydroxy, amino, N-lower alkylamino, formyl, lower alkylcarbonyl, arylcarbonyl, carboxyl, lower alkoxycarbonyl, formylamino, lower alkylcarbonylamino, carbamoyl, N-lower alkylcarbamoyl, N,N-di-lower alkylaminocarbonyl, aminosulfonyl, (N-lower alkylamino)sulfonyl, (N,N-di-lower alkylamino)sulfonyl, (N-lower alkylamino)sulfonylamino, aminosulfonylamino, (N,N-di-lower alkylamino)sulfonylamino, lower alkylsulfonylamino, and aryl, more preferably halogen, hydroxy, amino, lower alkylcarbonylamino, N,N-di-lower alkylaminocarbonyl, (N-lower alkylamino)sulfonyl, aminosulfonylamino, (N,N-di-lower alkylamino)sulfonylamino, and lower alkylsulfonylamino.

In R 2 , R 3 , R 4 , and R 5 which represent arylsulfonyl, one or more hydrogen atoms on the group may be substituted, and the substituent includes for example a group selected from the group consisting of lower alkyl, halogen, nitro, cyano, lower cycloalkyl, lower alkylthio, lower alkoxy, hydroxy, amino, N-lower alkylamino, formyl, lower alkylcarbonyl, arylcarbonyl, carboxyl, lower alkoxycarbonyl, formylamino, lower alkylcarbonylamino, carbamoyl, N-lower alkylcarbamoyl, N,N-di-lower alkylaminocarbonyl, aminosulfonyl, (N-lower alkylamino)sulfonyl, (N,N-di-lower alkylamino)sulfonyl, (N-lower alkylamino)sulfonylamino, aminosulfonylamino, and (N,N-di-lower alkylamino)sulfonylaminol more preferably lower alkyl.

Furthermore, in R 2 , R 3 , R 4 , and R 5 which represent N-lower alkylaminosulfonyl, one or more hydrogen atoms on the group may be substituted, and the substituent includes for example a group selected from the group consisting of halogen, nitro, cyano, lower cycloalkyl, loweralkylthio, lower, alkoxy, hydroxy, amino, N-lower alkylamino, formyl, lower, alkylcarbonyl, arylcarbonyl, carboxyl, lower alkoxycarbonyl, formylamino, lower alkylcarbonylamino, carbamoyl, N-lower alkylcarbamoyl, N,N-di-lower alkylaminocarbonyl, aminosulfonyl, (N-lower alkylamino)sulfonyl, (N,N-di-lower sulfonyl, (N-lower alkylamino)sulfonylamino, aminosulfonylamino, (N,N-di-lower alkylamino)sulfonylamino, and aryl (in which one or more hydrogen atoms on the aryl may be substituted, and the substituent includes for example a group selected from the group consisting of lower alkyl, halogen, nitro, cyano, lower cycloalkyl, lower alkylthio, lower alkoxy, hydroxy, amino, N-lower alkylamino, formyl, lower alkylcarbonyl, arylcarbonyl, carboxy, lower alkoxycarbonyl, formylamino, lower alkylcarbonylamino, carbamoyl, N-lower alkylcarbamoyl, N,N-di-lower alkylaminocarbonyl, aminosulfonyl, (N-lower alkylamino)sulfonyl, (N,N-di-lower allkylamino)sulfonyl, (N-lower alkylamino)sulfonylamino, aminosulfonylamino, and (N,N-di-lower alkylamino)sulfonylamino), more preferably lower alkoxy, hydroxy, and aryl (which may be substituted by amino).

Furthermore, in R 2 , R 3 , R 4 , and R 5 which represent N-di-loweralkylaminosulfonyl, one or more hydrogen atoms on the group may be substituted, and the substituent includes for example a group selected from the group consisting of halogen, nitro, cyano, lowercycloalkyl, lower alkylthio, lower alkoxy, hydroxy, amino, N-lower alkylamino, formyl, lower alkylcarbonyl, arylcarbonyl, carboxy, lower alkoxycarbonyl, formylamino, lower alkylcarbonylamino, carbamoyl, N-lower alkylcarbamoyl, N,N-di-lower alkylaminocarbonyl, aminosulfonyl, (N-lower alkylamino)sulfonyl, (N,N-di-lower alkylamino)sulfonyl, (N-lower alkylamino)sulfonylamino, aminosulfonylamino, (N,N-di-lower alkylamino)sulfonylamino, and aryl.

Furthermore, in R 2 , R 3 , R 4 , and R 5 which represent aryl, one or more hydrogen atoms on the group may be substituted, and the substituent includes for example a group selected from the group consisting of lower alkyl, halogen, nitro, cyano, lower cycloalkyl, lower alkylthio, lower alkoxy, hydroxy, amino, N-lower alkylamino, formyl, lower alkylcarbonyl, arylcarbonyl, carboxy, lower alkoxycarbonyl, formylamino, lower alkylcarbonylamino, carbamoyl, N-lower alkylcarbamoyl, N,N-di-lower alkylaminocarbonyl, aminosulfonyl, (N-lower alkylamno)sulfonyl, (N,N-di-lower alkylamino)sulfonyl, (N-lower alkylamino)sulfonylamino, aminosulfonylamino, and (N,N-di-lower alkylamino)sulfonylamino, more preferably lower alkylcarbonyl.

Examples of a five- or six-membered aromatic heterocyclic ring having one or more hetero atoms selected from nitrogen, oxygen and sulfur atoms represented by R 2 , R 3 , R 4 , and R 5 include thiazolyl, imidazolyl, oxazolyl, pyridyl, pyrrolyl, pyrazinyl, and pyrimidinyl, more preferably thiazolyl. On these groups, one or more hydrogen atoms may be substitutled, and the substituent includes for example lower alkyl, halogen, lower alkoxy, hydroxy, and amino.

›DETAILED DESCRIPTION OF THE INVENTION · 3 of 17

R represents a group which may be hydrolyzed in organisms, preferably an ester residue Examples of the group include C 1-10 alkyl, arylcarbonyloxy-lower alkyl group, aryl lower alkyloxy-lower-alkylcarbonyloxy-lower alkyl group, lower alkylcarbonyloxy-lower-alkyl, lower cycloalkylcarbonyloxy-lower-alkyl, lower cycloalkyl-lower-alkylcarbonyloxy-lower-alkyl, dicyclohexylmethylcarbonyloxy-lower-alkyl, adamantylcarbonyloxy-lower-alkyl, lower alkyloxycarbonyloxy-lower-alkyl, lower cycloalkyloxycarbonyloxy-lower-alkyl, (lower cycloalkyloxycarbonyloxy)(lower-cycloalkyl)methyl, lower-alkyl, adamantyloxlycarbonyloxy-lower-alkyl, 2-indanyloxycarbonyloxy-lower-alkyl, aryl-lower-alkyloxy carbonyloxy-lower-alkyl, aryloxycarbonyloxy-lower-alkyl in which the aromatic ring may be substituted, 5-indanyloxycarbonyloxoy-lower-alkyl in which the aromatic ring maybesubstituted, 2-oxo-5-lower alkyl-1,3-dioxolen-4-ylmethyl, 3-phthalidyl in which the aromatic ring may be substituted, or 2-(3-phthalidylidene)ethyl in which the aromatic ring may be substituted.

According to another preferred embodiment of the present invention, R preferably represents

C 1-10 alkyl,

arylcarbonyloxy-lower alkyl,

aryl lower alkyloxy-lower-alkylcarbonyloxy-lower alkyl group,

lower cycloalkyl-lower alkylcarbonyloxy-lower-alkyl,

dicyclohexylmethylcarbonyloxy-lower-alkyl,

adamantylcarbonyloxy-lower-alkyl

(lower cycloalkyloxycarbonylobxy)(lower-cycloalkyl)methyl,

lower cycloalkylethoxycarbonyloxy-lower-alkyl,

adamantyloxlycarbonyloxy-lower-alkyl,

2-indanyloxycarbonyloxy-lower-alkyl,

aryl-lower-alkyloxycarbonyloxy-lower-alkyl,

aryloxycarbonyloxy-lower-alkyl in which the aromatic ring may be substituted, or

5-indanyloxycarbonyloxy-lower-alkyl.

According to another preferred embodiment of the present invention, R represents

benzoyloxymethyl,

1-(benzoyloxy)ethyl,

1-(2-methylbenzoyloxy)ethyl,

4-t-butylbenzoyloxymethy,

2,4,6-trimethylbenzoyloxymethyl,

4-(N,N-di-n-propylaminosulfony)benzoyloxymethly,

1-[4-(N,N-di-n-propylaminosulfony)benzoyloxymethly]ethyl,

2-naphtylcarbonyloxymethyl,

1-adamantylcarbonyloxymethyl,

1-(1-adamantylcarbonyloxy)ethyl,

cyclohexyl(cyclohexyloxycarbonyloxy)methyl,

(1R,2S,5R)-(l)-menthyloxycarbonyloxymethyl,

(1S,2R,5S)-(d)-menthyloxycarbonyloxymethyl,

1-[(cyclohexylethoxy)carbonyloxy]ethyl,

2-adamantyloxycarbonyloxymethyl,

1-(2-phenyl-1-ethyloxycarbonyloxy)ethyl,

1-(4-methylphenoxycarbonyloxy)ethyl,

1-(2-methylphenoxycarobonyloxy)ethyl,

1-(2-ethylphenoxycarobonyloxy)ethyl,

1-[2-(2-propyl)phenoxycarobonyloxy]ethyl,

1-(2,4-dimethylphenoxycarobonyloxy)ethyl,

1-(2,5-dimethylphenoxycarobonyloxy)ethyl,

1-(3,5-dimethylphenokycarobonyloxy)ethyl,

1-(2,3,5-trimethylphenoxycarobonyloxy)ethyl,

1-(2,6-dimethylphenoxycarobonyloxy)methyl,

2-methyl-1-(phenoxycarbonyloxy)-1-propyl,

1-(2-methoxyphenoxycarobonyloxy)ethyl,

(1-naphthoxycarbonyloxy)ethyl,

(indan-5-yl)oxyearbonyloxymethyl,

1-((indan-5-yl)oxycarbonyloxy)methyl, and

1-((indan-5-yl)oxycarbonyloxy)-1-propyl.

Examples of the substitulents on the 2-indanyloxycarbonyloxy-lower-alkyl, 5-indanyloxycarbonyloxy-lower-alkyl, 3-phthalidyl, and 2-(3-phthalidylidene)ethyl include lower alkyl, halogen, nitro, cyano, lower cycloalkyl, lower allkylthio, lower alkoxy, hydroxy, amino, N-lower alkylamino, formyl, loweralkylcarbonyl arylcarbonyl, carboxy, lower alkoxycarbonyl, formylamino, lower, alkylcarbonylamino, carbamoyl, N-lower alkylcarbamoyl, N,N-di-lower alkylaminocarbonyl, aminosulfonyl, (N-lower alkylamino)sulfonyl, (N,N-di-lower alkylamino)sulfonyl, (N-lower alkylamino)sulfonylamino, aminosulfonylamino, (N,N-di-lower alkylamino)sulfonylamino, and aryl, more preferably lower alkoxy, hydroxy, formylamino, and carbamoyl.

One or more hydrogen atoms on the alkyl group of lower-alklycarbonyloxy-lower-alkyl, lower-alkyloxycarbonyloxy-lower-alkyl, and 2-oxo-5-lower alkyl-1,3-dioxolen-4-ylmethyl represented by R may be substituted, and the substituents include for example halogen, nitro, cyano, lower cycloalkyl, lower alkylthio, lower alkoxy, hydroxy, amino, N-lower alkylamino, formyl, lower alkylcarbonyl, arylcarbonyl, carboxy, lower alkoxycarbonyl, formylamino, lower alkylcarbonylamino, carbamoyl, N-lower alkylcarbamoyl, N,N-di-lower alkylaminocarbonyl, aminosulfonyl, (N-lower alkylamino)sulfonyl, (N,N-di-lower alkylamino)sulfonyl, (N-lower alkylamino)sulfonylamino, aminosulfonylamino, (N,N-di-lower alkylamino)sulfonylamino, lower-alkylsulfonylamino, and aryl, more preferably lower alkoxy, lower-cycloalkyl, and aryl.

One or more hydrogen atoms on the aryl group of arylcarbonyoxy lower alkyl, aryl lower alkyloxy lower alkylcarbonyloxy lower alkyl, aryl lower alkyloxycarbonyloxy lower alkyl, aryloxycarbonyloxy lower alkyl represented by R may be substituted, and the substituents include for example lower alkyl, halogen, nitro, cyano, lower cycloalkyl, lower alkylthio, lower alkoxy, hydroxy, amino, N-lower alkylamino, formyl, lower alkylcarbonyl, arylcarbonyl, carboxy, lower alkoxycarbonyl, formylamino, lower alkylcarbonylamino, carbamoyl, N-lower alkylcarbamoyl, N,N-di-lower alkylaminocarbonyl, aminosulfonyl, (N-lower alkylamino)sulfonyl, (N,N-di-lower alkylamino)sulfonyl, (N-lower alkylamino)sulfonylamino, aminosulfonylamino, (N,N-di-lower alkylamino)sulfonylamino, and aryl, more preferably lower alkyl, lower alkoxy, lower-cycloalkyl, and aryl.

One or more hydrogen atoms on the cycloalkyl group of lower cycloalkylcarbonyloxy-lower-alkyl, lower cycloalkyl-lower-alkylcarbonyloxy-lower-alkyl, lower cycloalkyloxycarbonyloxy-lower-alkyl, (lower cycloalkyloxycarbonyloxy) (lower-cycloalkyl)methyl, and lower cycloalkyl lower alkyloxycarbonyloy lower alkyl represented by R may be substituted, and the substituents include for example lower alkyl, halogen, nitro, cyano, lower alkylthio, lower alkoxy, hydroxy, amino, N-lower alkylamino, formyl, lower alkylcarbonyl, arylcarbonyl, carboxy, lower alkoxycarbonyl, formylamino, lower alkylcarbonylamino, carbamoyl, N-lower alkylcarbamoyl, N,N-di-lower alkylaminocarbonyl, aminosulfonyl, (N-lower alkylamino)sulfonyl, (N,N-di-lower alkylamino)sulfonyl, (N-lower alkylamino)sulfonylamino, aiinosulfonylamino, (N,N-di-lower alkylamino)sulfonylamino, and aryl, more preferably lower alkyl, lower alkoxy, and lower-cycloalkyl.

›DETAILED DESCRIPTION OF THE INVENTION · 4 of 17

The preferred compounds of the formula (I) according to the present invention include those in which

R 1 represents a hydrogen atom or a methyl group,

R 2 , R 3 , R 4 , and R 5 , either one of which represents the bonding to the 2-position on the carbapenem ring, and the other three of which may be the same or different, respectively represent

a hydrogen atom,

a halogen atom,

a cyano group,

a lower alkyl group which may be substituted,

a lower cycloalkyl group which may be substituted,

a lower alkylthio group,

an arylthio group,

a C 2-4 alkenyl group which may be substituted,

a formyl group,

a lower alkylcarbonyl group which may be substituted,

a lower alkylsulfonyl group,

an arylsulfonyl group which may be substituted,

an aminosulfonyl group,

an N-loweralkylaminosulfonyl group which may be substituted,

an N,N-di-lower alkylaminosulfonyl group which may be substituted,

a lower alkylsufinyl group,

an arylcarbonyl group,

an aryl group which may be substituted,

a lower alkoxyiminomethyl group,

a hydroxyiminomethyl group, or

a five- or six-membered aromatic heterocyclic ring having one or more hetero atoms selected from nitrogen, oxygen and sulfur atoms.

The preferred compounds of the formula (I) according to the present invention include those in which R 2 represents the bonding to the 2-position on the carbapenem ring. Among the compounds of formula (I) in which R 2 represents the bonding to the 2-position on the carbapenem ring, the preferred compounds include those in which

R 1 represents hydrogen or methyl,

R 3 , R 4 , and R 5 , which may be the same or different, and respectively represent

a hydrogen atom,

a cyano group,

a lower alkyl group in which one or more hydrogen atoms on the alkyl group may be substituted by groups selected from the group consisting of a halogen atom, a hydroxy group, an amino group, a formylamino group, a lower alkylcarbonylamino group, a carbamoyl group, and a lower alkylsulfonylamino group,

a lower-cycloalkyl group which may be substituted by a carbamoyl group,

a lower alkylthio group,

an arylthio group,

a C 2-4 alkenyl group in which one or more hydrogen atoms on the alkenyl group may be substituted by a lower alkylcarbonyl group or a lower alkoxy carbonyl group,

a formyl group,

a lower alkylcarbonyl group in which one or more hydrogen atoms on the alkyl group may be substituted by groups selected from the group consisting of a halogen atom, a hydroxy group, an amino group, a lower alkylcarbonylamino group, N,N-di-lower alkylaminocarbonyl group, an (N-lower alkylamino)sulfonylamino group, an (N,N-di-lower alkylamino)sulfonylamino group and a lower alkylsulfonylamino group,

a lower alkyl sulfonyl group,

an aryl sulfonyl group in which one or more hydrogen atoms on the aryl group may be substituted by a lower alkyl group,

an aminosulfonyl group,

an N-lower alkylaminosulfonyl group in which one or more hydrogen atoms on the alkyl group may be substituted by groups selected from the group consisting of a lower alkoxy group, a hydroxy group,

and an aryl group (in which one or more hydrogen atoms on the aryl group may be substituted by an amino group),

an N,N-di-lower alkylaminosulfonyl group,

a lower alkylsufinyl group,

an arylcarbonyl group,

an aryl group which may be substituted by a lower alkylcarbonyl group,

a lower alkoxyiminomethyl group,

a hydroxyiminomethyl group, or

a five- or six-membered aromatic heterocyclic ring having one or more hetero atoms selected from nitrogen, oxygen and sulfur

Among the compounds, more preferred compounds include those in which

R 1 represents methyl,

R 3 , R 4 , and R 5 , which may be the same or different, and respectively represent

a hydrogen atom,

a lower alkyl group which may be substituted by groups selected from the group consisting of a halogen atom, a hydroxy group,

an amino group, a formylamino group, a lower alkylcarbonylamino group, a carbamoyl group, a lower alkylsulfonylamino group, and

an aryl group,

a lower alkylthio group,

an arylthio group,

a lower alkylcarbonyl group which may be substituted by groups selected from the group consisting of a halogen atom, a hydroxy group, an amino group, a lower alkylcarbonylamino group,

N,N-di-lower alkylaminocarbonyl group, an (N-lower alkylamino)sulfonylamino group, an (N,N-di-lower alkylamino)sulfonylamino group and a lower alkylsulfonylamino group,

a lower alkyl sulfonyl group,

an aryl sulfonyl group which may be substituted by a lower alkyl group,

an aminosulfonyl group,

an N-lower alkylaminosulfonyl group which may be substituted by groups selected from the group consisting of a lower alkoxy group,

a hydroxy group, group (which may be substituted by

an amino group),

an N,N-di-lower alkylaminosulfonyl group

a lower alkylsufinyl group,

a hydroxyiminomethyl group, or

a five- or six-membered aromatic heterocyclic ring having one or more hetero atoms selected from nitrogen, oxygen and sulfur atoms.

Another preferred compounds include those in which

R 1 represents methyl,

R 2 represents the bonding to the 2-position on the carbapenem ring,

R 3 and R 4 represent a hydrogen atom,

R 5 represents a lower alkylthio group or a lower alkylsulfonyl group, and

R represents a hydrogen atom or a group which may be hydrolyzed in organisms. Among these compounds, more preferred compounds include those in which

R 5 represents methylthio or methylsulfonyl.

Another preferred compounds include those in which

R 1 represents methyl,

R 2 represents the bonding to the 2-position on the carbapenem ring,

R 3 and R 4 represent a hydrogen atom,

R 5 represents a lower alkylcarbonyl group (in which one or more hydrogen atoms on the alkyl group maybe substituted by groups selected from the group consisting of a halogen atom, a hydroxy group, an amino group, a lower alkylcarbonylamino group,

N,N-di-lower alkylaminocarbonyl group, an (N-lower alkylamino)sulfonylamino group, an (N,N-di-lower alkylamino)sulfonylamino group and a lower alkylsulfonylamino group), a lower alkyl group substituted by a lower alkylcarbonylamino group, an N,N-di-lower alkylaminosulfonyl group, or a lower alkylsulfinyl group. Another preferred compounds include those in which

›DETAILED DESCRIPTION OF THE INVENTION · 5 of 17

R 1 represents methyl,

R 2 represents the bonding to the 2-positionlon the carbapenem ring,

R 3 and R 4 represent a hydrogen atom,

R 5 represents a lower alkyl group substituted by a lower alkylcarbonylamino group,

those in which

R 1 represents methyl,

R 2 represents the bonding to the 2-position on the carbapenem ring,

R 3 and R 4 represent a hydrogen atom,

R 5 represents an N,N-di-lower alkylaminosulfonyl group,

those in which n

R 1 represents methyl,

R 2 represents the bonding to the 2-position on the carbapenem ring,

R 3 and R 4 represent a hydrogen atom,

R 5 represents an N,N-dimethylaminosulonyl group,

those in which

R 1 represents methyl,

R 2 represents the bonding to the 2-position, on the carbapenem ring,

R 3 represents a hydrogen atom,

R 4 represents a lower alkyl group,

R 5 represents a lower alkylcarbonyl group which may be substituted by a hydroxy group,

those in which

R 1 represents methyl,

R 2 represents the bonding to the 2-position on the carbapenem ring,

R 3 represents a hydrogen atom,

R 4 represents a lower alkyl group, and

R 5 represents a lower alkylsulfonyl group,

those in which

R 1 represents methyl,

R 2 represents the bonding to the 2-position on the carbapenem ring,

R 3 represents a hydrogen atom,

R 4 represents methyl, and,

R 5 represents methylsulfonyl.

those in which

R 1 represents methyl,

R 2 represents the bonding to the 2-position on the carbapenem ring,

R 3 and R 4 represent a hydrogen atom, and

R 5 represents a lower alkylsulfinyl group,

those in which

R 1 represents methyl,

R 2 represents the bonding to the 2-position on the carbapenem ring,

R 3 and R 4 represent a hydrogen atom, and

R 5 represents methylsulfinyl group.

Another preferred compounds include those in which

R 1 represents a hydrogen atom or a methyl group,

R 2 , R 3 , R 4 , and R 5 , except the one which represents the bonding to the 2-position on the carbapenem ring, which may be the same or different, and respectively represent

a hydrogen atom,

a lower alkyl group which be substituted,

an arylthio group,

a lower alkylcarbonyl group which may be substituted,

an arylsulfonyl group which may be substituted,

an N-loweralkylaminosulfonyl group which may be substituted,

an N,N-di-lower alkylaminosulfonyl group which may be substituted,

an N-lower alkoxy-N-lower alkylaminosulfonyl group,

a lower alkylsufinyl group,

a arylsulfinyl group,

an aminosulfinyl group, or

a five- or six-membered aromatic heterocyclic ring having one or more hetero atoms selected from nitrogen, oxygen and sulfur atoms,

those in which

R 1 represents a hydrogen atom or a methyl group,

R 2 , R 3 , R 4 , and R 5 , except the one which represents the bonding to the 2-position on the carbapenem ring which may be the same or different, and respectively represent,

a hydrogen atom,

a lower alkyl group in which one or more hydrogen atoms on the alkyl group may be substituted by groups selected from the group consisting of a halogen atom, a hydroxy group, an amino group,

an N-lower alkylamino group, a formylamino group, a lower alkylcarbonylamino group, a carbamoyl group, and a lower alkylsulfonylamino group,

an arylthio group,

a lower alkylcarbonyl group, in which one or more hydrogen atoms on the alkyl group may be substituted by groups selected from the group consisting of a halogen atom, a hydroxy group, an amino group, a lower alkylcarbonlyamino group, N,N-di-lower alkylaminocarbonyl group, an (N-lower alkylamino)sulfonylamino group, an (N,N-di-lower alkylamino)sulfonylamino group and a lower alkylsulfonylamino group,

a arylsulfonyl group substituted by a lower alkyl group, an N-lower alkylaminosulfonyl group in which one or more hydrogen atoms on the alkyl group may be substituted by groups selected from the group consisting of a lower alkoxylgroup, a hydroxy gorup,

and an aryl group (which may be substituted by an amino group),

an N,N-di-lower alkylaminosulfonyl group

a lower alkylsufinyl group, or

a five- or six-membered aromatic heterocyclic ring having one or more hetero atoms selected from nitrogen, oxygen and sulfur atoms, and

those in which

R 1 represents a hydrogen atom or a methyl group,

R 2 , R 3 , R 4 , and R 5 , except the one which represents the bonding to the 2-position on the carbapenem ring, which may be the same or different, and respectively represent

a hydrogen atom,

a lower alkyl group, in which one or more hydrogen atoms on the alkyl, group may be substituted by groups selected from the group consisting of a halogen atom, a nitro group, a cyano group, a lower cycloalkyl group, a lower alkylthio group, a lower alkoxy group, a hydroxy group, an amino group, an N-lower alkylamino group, a formyl group, a lower alkylcarbonyl group, an aryl carbonyl group, a carboxyl group, a lower alkoxycarbonyl group, a formylamino group, a lower alkylcarbonylamino group, a carbamoyl group an N-lower alkylcarbamoyl group, an N,N-di-lower alkylaminocarbonyl group, an aminosulfonyl group, an (N-lower alkylamino)sulfonyl group, an (N,N-di-lower alkylamino)sulfonyl group, an (N-lower alkylamino) sulfonylamino group, an aminosulfonylamino group, an (N,N-di-lower alkylamino)sulfonylamino group, a lower alkylsulfonylamino group and an aryl group, or

an arylthio group.

According to the preferred embodiment of the present invention, R preferably represents

C 1-10 alkyl which may be substituted,

arylcarbonyloxy-lower-alkyl group which may be substituted, aryl lower alkyloxy-lower-alkylcarbonyloxy-lower alkyl group which may be substituted,

lower cycloalkyl-lower-alkylcarbonyloxy-lower-alkyl which may be substituted,

dicyclohexylmethylcarbonyloxy-lower-alkyl which may be substituted,

adamantylcarbonyloxy-lower-alkyl which may be substituted, (lower cycloalkyloxycarbonyloxy) (lower-cycloalkyl)methyl which may be substituted,

lower cycloalkyl-ethoxycarbonyloxy-lower-alkyl which may be substituted,

adamantyloxlycarbonyloxy-lower-alkyl which may be substituted,

2-indanyloxycarbonyloxy-lower-alkyl which may be substituted,

aryl-lower-alkyloxycarbonyloxy-lower-alkyl which may be substituted, or

5-indanyaoxycarbonyloxy-lower-alkyl which may be substituted.

›DETAILED DESCRIPTION OF THE INVENTION · 6 of 17

According to another preferred embodiment of the present invention, R preferably represents

C 1-10 alkyl,

arylcarbonyloxy-lower alkyl,

aryl lower alkyloxy-lower-alkylcarbonyloxy-lower alkyl group,

lower cycloalkyl-lower alkylcarbonyloxy-lower-alkyl,

dicyclohexylmethylcarbonyloxy-lower-alkyl,

adamantylcarbonyloxy-lower-alkyl,

(lower cycloalkyloxycarbonyloxy)(lower-cycloalkyl)methyl,

lower cycloalkylethoxycarbohyloxy-lower-alkyl,

adamantyloxycarbonyloxy-lower-alkyl,

indanyloxycarbonyloxy-lower-alkyl,

aryl-lower-alkyloxycarbonyloxy-lower-alkyl,

aryloxycarbonyloxy-lower-alkyl in which the aromatic ring may be substituted, or

5-indanyloxycarbonyloxy-lower alkyl.

Among them, R preferably represents

C 1-10 alkyl,

arylcarbonyloxy-lower-alkyl,

aryl lower alkyloxy-lower-alkylcarbonyloxy-lower-alkyl group,

lower cycloalkylcarbonyloxy-lower-alkyl,

lower cycloalkyl-lower-alkylcarbonyloxy-lower-alkyl,

dicyclohexylmethylcarbonyloxy-lower-alkyl,

adamantylcarbonyloxy-lower-alkyl,

lower alkyloxycarbonyloxy-lower-alkyl,

lower cycloalkyloxycarbonyloxy-lower-alkyl,

(lower cycloalkyloxycarbonyloxy)(lower cycloalkyl)methyl,

lower cycloalkyl-lower-alkyloxycarbonyloxy-lower-alkyl,

adamantyloxycarbonyloxy-lower-alkyl,

2-indanyloxycarbonyloxy-lower-alkyl in which the aromatic ring may be substituted,

aryl-lower-alkyloxycarbonyloxy-lower-alkyl, aryloxycarbonyloxy-lower-alkyl,

5-indanyloxycarbonyloxy-lower-alkyl in which the aromatic ring may be substituted. One or more hydrogen atoms on the alkyl group,

the lower cycloalkyl group or the aryl group on the above groups may be substituted.

The compound represented by the formula (I) according to the present invention can exist as a salt, and the preferred salt is a pharmacologically acceptable salt. Such a salt includes for example inorganic salts such as lithium, sodium, potassium, calcium, or magnesium salts, an ammonium salt, salts with organic bases such as triethylamine or diisopropylethylamine, salts with mineral acids such as hydrochloric acid, sulfuric aicd, phosphoric acid, or nitric acid, or salts with organic acids such as aceticacid, carbonic acid, citric acid, malic acid, oxalic acid, or methanesulfonic acid, preferably an inner salt, or sodium or potassium salt.

Specific examples of carbapenem derivatives represented by formula (I) according to the present invention include, but are not limited to

1. Sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-propionylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

2. Pivaloyloxymethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-propionylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

3. Sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-hydroxyiminomethylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a geometrical isomer derived from a starting compound as a low-polarity oxime isomer)

4. Sodium (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methoxyiminomethylimidazo[5,1-b]thiazol-3-yl)-1-carbapen-2-em-3-carboxylate (a geometrical isomer derived from a starting compound as a low-polarity oxime isomer)

5. Pivayloxymethyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-metholxyiminomethylimidazo[5,1-b]thiazol-3-yl)-1-carbapen-2-em-3-carboxylate (a geometrical isomer derived from a starting compound as a low-polaity oxime isomer)

6. Sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-pivaloylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

7. Pivaloyloxymethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-pivaloylimidazo[5,1]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

8. Sodium (5R,6S)-2-(7-acetyl-3-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

9. Pivaloyloxymethyl (5R,6S)-2-(7-acetyl-3-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

10. Sodium (1S,5R,6S)-2-[7-(2-formylaminopropionyl)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-metyl-1-carbapen-2-em-3-carboxylate (a high-polarity isomer)

11. Sodium (1S,5R,6S)-2-[7-(2-formylaminopropionyl)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a low-polarity isomer)

12. Sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-isobutyrylimidazo[5,1-b]thiazol-2-yl)-1-1-methyl-1-carbapen-2-em-3-carboxylate

13. Pivaloyloxymethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-isobutyrylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

14. Sodium (5R,6S)6-((1R)-1-hydroxyethyl)-2-(7-propionylimidazo[5,1-b]thiazol-3-yl)-1-carbapen-2-em-3-carboxylate

15. Sodium (5R,6S)-2-(7-acetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

16. Pivaloyloxymethyl (5R,6S)-2-(7-acetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

17. Sodium (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-isobutyrylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

18. Pivaloyloxymethyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-isobutyrylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

19. Sodium (1S,5R,6S)-2-(7-acetyl-5-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

20. Pivaloyloxymethyl (1S,5R,6S)-2-(7-acetyl-5-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

21. Sodium (1S,5R,6S)-2-(7-acetyl-3-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

22. Pivaloyloxymethyl (1S,5R,6S)-2-(7-acetyl-3-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxy-ethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

23. Sodium (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

24. Sodium (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-3-yl))-1-carbapen-2-em-3-carboxylate

25. Sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-37-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

26. Sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfinylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

›DETAILED DESCRIPTION OF THE INVENTION · 7 of 17

27. Sodium (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-propionylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

28. Pivaloyloxymethyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-propionylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

29. Pivaloyloxymethyl (5R,6S)-2-(7-acetylimidazo[5,1-b]thiazol-3-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

30. Sodium (1S,5R,6S)-2-(7-ethanesulfonylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

31. Sodium (1S,5R,6S)-6-((1R)-1-hlydroxyethy)-1-methyl-2-(7-N-methylsulfamoylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

32. Sodium (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-N-methylsulfamoylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

33. Sodium (5R,6S)-2-(7-acetyl-5-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

34. Sodium (5R,6S)-2-(7-ethanesulfonylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

35. Sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-p-toluenesulfonylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

36. Sodium (5R,6S)-2-(7-hydroxyacetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

37. Sodium (1S,5R,6S)-2-(7-benzloylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

38. Sodium (5R,6S)-2-(7-hydroxyacetylimidazo[5,1-b]thiazol-3-yl)-6-(1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

39. Sodium (5R,6S)-2-(7-benzoylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

40. Sodium (1S,5R,6S)-2-[7-[N-(4-aminobenzyl)sulfamoyl]imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

41. Sodium (1S,5R,6S)-2-(7-fluoroimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

42. Sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-[7-[N-(2-hydroxyethyl)-N-methylsulfamoyl]imidazo[5,1-b]thiazol-2-yl]-1-methyl-1-carbapen-2-em-3-carboxylate

43. Sodium (1S,5R,6S)-2-(7-acetylaminoacetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxymethyl-1-carbapen-2-em-3-carboxylate

44. Sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonyl-5-methylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

45. Sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfinyl-5-methylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomners)

46. 1-(Ethoxycarbonyloxy)ethyl (1S,5R,6S)-2-(7-acetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxy-ethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

47. 1-(Isopropoxycarbonyloxy)ethyl (1S,5R,6S)-2-(7-acetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

48. 1-(Cyclohexyloxycarbonyloxy)ethyl (1S,5R,6S)-2-(7-acetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a

49. Cyclohexyloxycarbonyloxymethyl (1S,5R,6S)-2-(7-acetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

50. 3-Phthalidyl (1S,5R,6S)-2-(7-acetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

51. 1-(Acetoxy)ethyl (1S,5R,6S)-2-(7-acetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

52. (5-Methyl-2-oxo-1,3-dioxolen-4-yl)methyl (1S,5R,6S)-2-(7-acetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

53. Sodium (1S,5R,6S)-2-(7-N-acetylaminomethylimidazo-[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

54. Pivaloyloxymethyl (1S,5R,6S)-2-(7-N-acetylaminomethylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

55. 1-(Acetoxy)ethyl (1S,5R,6S)-2-(7-N-acetylaminomethylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

56. 1-(Cyclohexyloxycarbonyloxy)ethyl (1S,5R,6S)-2-(7-N-acetylaminomethylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

57. 3-Phthalidyl (1S,5R,6S)-2-(7-N-acetylaminomethylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

58. (5-Methyl-2-oxo-1,3-dioxolen-4-yl)methyl (1S,5R,6S)-2-(7-N-acetylaminomethylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

59. 1-[(Cyclohexylmethoxy)carbonyloxy]ethyl (1S,5R,6S)-2-(7-N-acetylaminomethylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

60. (1R,2S,5R)-(1)-Menthyloxycarbonyloxymethyl (1S,5R,6S)-2-(7-N-acetylaminomethylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

61. 1-(Cyclohexyloxycarbonyloxy)-n-propyl (1S,5R,6S)-2-(7-N-acetylaminomethylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

62. Sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

63. Pivaloyloxymethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

64. 1-(Acetoxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

65. 1-(Cyclohexyloxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazod[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

66. 3-Phthalidyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture, of diastereomers)

67. (5-Methyl-2-oxo-1,3-dioxolen-4-yl)methyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonyl-imidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

›DETAILED DESCRIPTION OF THE INVENTION · 8 of 17

68. 1-[(Cyclohexylmethoxy)carbonyloxy]ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

69. (1-Methylcyclohexan-1-yl)carbonyloxymethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

70. 1-(Cyclohexyloxycarbonyloxy)-n-propyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

71. Sodium (1S,5R,6S)-2-(7-hydroxyacetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-;

72. Pivaloyloxymethyl (1S,5R,6S)-2-(7-hydroxyacetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

73. 1-(Acetoxy)ethyl (1S,5R,6S)-2-(7-hydroxyacetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

74. 1-(Cyclohexyloxycarbonyloxy)ethyl (1S,5R,6S)-2-(7-hydroxyacetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

75. 3-Phthalidyl (1S,5R,6S)-2-(7-hydroxyacetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

76. (5-Methyl-2-oxo-1,3-dioxolen-4-yl)methyl (1S,5R,6S)-2-(7-hydroxyacetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

77. (1-Methylcyclohexan-1-yl)carbonyloxymethyl (1S,5R,6S)-2-(7-hydroxyacetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

78. 1-[(Cyclohexylmethoxy)carbonyloxy]ethyl (1S,5R,6S)-2-(7-hydroxyacetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

79. 1-(Cyclohexyloxycarbonyloxy)-n-propyl (1S,5R,6S)-2-(7-hydroxyacetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

80. Sodium (1S,5R,6S)-2-[7-(N,N-dimethylcarbamoyl)-acetylimidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

81. Pivaloyloxymethyl (1S,5R,6S)-2-[7-(N,N-dimethylcarbamoyl)acetylimidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

82. (1-Methylcyclohexan-1-yl)carbonyloxymethyl (1S,5R,6S)-2-[7-(N,N-dimethylcarbamoyl)acetylimidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

83. 1-(Cyclohexyloxycarbonyloxy)ethyl (1S,5R,6S)-2-[7-(N,N-dimethyldarcamoyl)acetylimidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

84. 3-Phthalidyl (1S,5R,6S)-2-[7-(N,N-dimethylcarbamoyl)acetylimidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

85. (5-Methyl-2-oxo-1,3-dioxolen-4-yl)methyl (1S,5R,6S)-2-[7-(N,N-dimethylcarbamoyl)acetylimidazo-[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

86. 1-[(Cyclohexylmethoxy)carbonyloxy]ethyl (1S,5R,6S)-2-[7-(N,N-dimethylcarbamoyl)acetylimidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

87. 1-(Cyclohexyloxycarbonyloxy)-n-propyl (1S,5R,6S)-2-[7-(N,N-dimethylcarbamoyl)acetylimidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

88. Sodium (1S,5R,6S)-2-[7-(N,N-dimethylsulfamoyl)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em -3-carboxylate

89. (1S,5R,6S)-2-[7-(N,N-dimethylsulfamoyl)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylatepivaloyloxymethyl

90. (1-Methylcyclohexan-1-yl)carbonyloxymethyl (1S,5R,6S)-2-[7-(N,N-dimethylsulfamoyl)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

91. 1-(Cyclohexyloxycarbonyloxy)ethyl (1S,5R,6S)-2-[7-(N,N-dimethylsulfamoyl)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

92. 3-Phthalidyl (1S,5R,6S)-2-[7-(N,N-dimethylsulfamoyl)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

93. (5-Methyl-2-oxo-1,3-dioxolen-4-yl)methyl (1S,5R,6S)-2-[7-(N,N-dimethylsulfamoyl)imidazo[5,1-b]thiazol-2-yl]-6-((R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

94. 1-[(Cyclohexylmethoxy)carbonyloxy]ethyl (1S,5R,6S)-2-[7-(N,N-dimethylsulfamoyl)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em -3-carboxylate (a mixture of diastereomers)

95. ((Cyclohexyloxycarbonyloxy)-n-propyl (1S,5R,6S)-2-[7-(N,N-dimethylsulfamoyl)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

96. Sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methoxycarbonylimidazo[5,1-b ]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

97. Sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-[7-(N-methoxy-N-methylsulfamoyl)imidazo[5, i1-b]thiazol-2-yl]-1-methyl-1-carbapen-2-em-3-carboxylate

98. Sodium (1S,5R,6S)6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-trifluoroacetylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

99. Sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-sulfamoylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate 100. Sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-[7-(2-(E)-methoxycarbonylvinyl)imidazo[5,1-b]thiazol-2-yl]1-methyl-1-carbapen-2-em-3-carboxylate

101. Sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-[7-(2-(Z)-methoxycarbonylvinyl)imidazo[5,1-b]thiazol-2-yl]-1-methyl-1-carbapen-2-em-3-carboxylate

102. Sodium (1S,5R,6S)-6-((1R)-1-hydroxyethy)-1-methyl-2-[7-(thiazol-4-yl)imidazo[5,1-b]thiazol-2-yl]-1-carbapen-2-em-3-carboxylate

103. Sodium (1S,5R,6S)-2-(7-hydroxyacetyl-5-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

›DETAILED DESCRIPTION OF THE INVENTION · 9 of 17

104. Sodium (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonyl-5-methylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

105. Sodium (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfinyl-5-methylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

106. Sodium (5R,6S)-2-(7-hydroxyacetyl-5-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxy-ethyl)-1-carbapen-2-em-3-carboxylate

107. Pivaloyloxymethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonyl-5-methylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

108. Sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylaminoacetylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

109. Sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(5-methyl-7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

110. Sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-[7-(methanesulfonylaminomethyl)imidazo[5,1-b]thiazol-2-yl]-1-methyl-1-carbapen-2-em-3-carboxylate

111. Sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

112. Sodium (5R,6S)-2-(7-dimethylaminosulfonyl-imidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxy-ethyl)-1-carbapen-2-em-3-carboxylate

113. Sodium (5R,6S)-2-(7-aminosulfonylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

114. Sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-[7-((E)-3-oxo-1-buten-1-yl)imidazo[5,1-b]thiazol-2-yl]-1-carbapen-2-em-3-carboxylate

115. Sodium (1S,5R,6S)-2-(7-formyl-5-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

116. Sodium (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

117. Sodium (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfinylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

118. Sodium (5R,6S)-2-[7-(N,N-dimethylaminosulfonylamino)acetylimidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

119. Sodium (1S,5R,6S)-2-[7-(N,N-dimethylaminosulfonylamino)acetylimidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

120. Sodium (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(5-methyl-7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

121. Sodium (1S,5R,6S)-2-(7-aminoacetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

122. Sodium (1S,5R,6S)-2-(7-aminiomethylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

123. Sodium (1S,5R,6S)-2-[7-(2-aminoethanesulfonylamino)acetylimidozo[5,1-b]thiazol-2-yl]-6-((1R)-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

124. Sodium (5R,6S)-2-[7-(2-aminoethanesulfonyl-amino)acetylimidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

125. Sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(5-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

126. Sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(5-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

127. Sodium (1S,5R,6S)-2-[5,1-bis (methylthio)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

128. Sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-phenylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

129. Sodium (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methylthioimidazo[5,1-b]thiazol-3-yl)-1-carbapen-2-em-3-carboxylate

130. Sodium (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-phenylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

131. Sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(3-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

132. Sodium (1S,5R,6S)-2-(7-ethylthioimidazo-[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

133. Sodium (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(3-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

134. Sodium (5R,6S)-2-(7-ethylthioimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

135. Sodium (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(3-methyl-7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

136. Sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfinyl-5-methylthioimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

137. Sodium (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(3-hydroxymethyl-7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

138. Sodium (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(3-phenylimidazo[5,1-b]thiazol-2-yl)-71-carbapen-2-em-3-carboxylate

139. Sodium (5R,6S)-2-(7-aminoacetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

140. Sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(5-methanesulfinylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

141. Sodium (1S,5R,6S)-2-(5,7-dimethanesulfinyl-imidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxy-ethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

142. Sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(5-methanesulfinyl-7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

143. Sodium (1S,5R,6S)-2-[5,7-bis (methane-sulfonyl)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

144. Sodium (5R,6S)-2-(3-aminomethylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

145. Sodium (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(3-hydroxymethylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

146. Sodium (5R,6S)-2-[5,7-bis(methylthio)-imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

147. Sodium (1S,5R,6S)-2-(5-acetyl-7-methylthioimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

148. Sodium (1S,5R,6S)-2-[3,7-bis (methylthio)-imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl-1-carbapen-2-em-3-carboxylate

›DETAILED DESCRIPTION OF THE INVENTION · 10 of 17

149. Sodium (1S,5R,6S)-2-(5-acetyl-7-methanesulfonylimidazo[5,1-b]thiazol)-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

150. Sodium (1S,5R,6S)-2-(5-bromo-7-methylthioimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

151. Sodium (5R,6S)-2-(5-acetyl-7-methylthioimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

152. Sodium (1S,5R,6S)-2-(5-cyano-7-methylthioimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

153. Sodium (5R,6S)-2-[3,7-bis (methylthio)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

154. Sodium (1S,5R,6S)-2-(5-chloro-7-methylthioinidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

155. Sodium (5R,6S)-2-(5-cyano-7-methylthioimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

156. Sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-[7-(1-propyl)thioimidazo[5,1-b]thiazol-2-yl]-1-carbapen-2-em-3-carboxylate

157. Sodium (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-(1-propyl)thioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

158. Sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-isopropylthioimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbepen-2-em-3-carboxylate

159. Sodium (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-isopropylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

160. 1-Methylcyclohexylcarbonyloxymethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonyl-5-methylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

161. 1-(Cyclohexyloxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonyl-5-methylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

162. Cyclohexyloxycarbonyloxymethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonyl-5-methylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

163. 3-Phthalidyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methiinesulfonyl-5-methyl-imidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

164. 5-Methyl-2-oxo-1,3-dioxolen-4-ylmethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonyl-5-methylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

165. (Z)-2-(3-Phthalidylidene)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonyl-5-methylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

166. 1-(Ethoxycarbonyloxy)ethyl (1S,5R,6S)-2-(7-acetyl-5-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

167. 1-(Cyclohexyloxycarbohyloxy)ethyl (1S,5R,6S)-2-(7-acetyl-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

168. Cyclohexyloxycarbonyloxymethyl (1S,5R,6S)-2-(7-acetyl-5-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

169. 3-Phthalidyl (1S,5R,6S)-2-(7-acetyl-5-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

170. 5-Methyl-2-oxo-1,3-dioxolen-4-ylmethyl (1S,5R,6S)-2-(7-acetyl-5-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

171. Cyclopentyloxycarbonyloxymethyl (1S,5R,6S)-2-(7-acetyl-5-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

172. 1-(Pivaloyloxy)ethyl (1S,5R,6S)-2-(7-acetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

173. 1-Methylcyclohexylcarbonyloxymethyl (1S,5R,6S)-2-(7-acetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

174. Cyclohexylcarbonyloxymethyl (1S,5R,6S)-2-(7-acetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

175. 1-(Cyclohexylcarbonyloxy)ethyl (1S,5R,6S)-2-(7-acetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

176. Hexanoyloxymethyl (1S,5R,6S)-2-(7-acetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

177. 2-Ethylbutyryloxymethyl (1S,5R,6S)-2-(7-acetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

178. Cyclopentyloxycarbonyloxymethyl (1S,5R,6S)-2-(7-acetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-carbapen-2-em-3-carboxylate

179. 1-(3-Pentyloxycarbonyloxy)ethyl (1S,5R,6S)-2-(7-acetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

180. 3-Pentyloxycarbonyloxymethyl (1S,5R,6S)-2-(7-acetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

181. Cyclohexylmethoxycarbonyloxymethyl (1S,5R,6S)-2-(7-acetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

182. 1-(Isobutyryloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

183. 1-(Pivaloyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

184. Hexanoyloxymethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

185. Cyclohexylcarbonyloxethyl (1S5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonyl-imidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

186. Cyclohexylacetoxymethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

187. Dicyclohexylacetoxymethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonyl-imidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

188. 1-(1-Methylcyclohexylcarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

›DETAILED DESCRIPTION OF THE INVENTION · 11 of 17

189. 1-Adamantylcarbonyloxymethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonyl-imidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

190. 1-(1-Adamantylcarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonyl-imidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

191. 1-(Benzoyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

192. 4-(2-Propyl)benzoyloxymethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonyl-imidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

193. 4-n-Butylbenzoyloxymethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonyl-imidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

194. 4-Phenylbenzoyloxymethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

195. 4-t-Butylbenzoyloxymethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonyl-imidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

196. 1-(4-t-Butylbenzoyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonyl-imidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

197. 2,4,6-Trimethylbenzoyloxymethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonyl-imidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

198. 1-(2-Propyloxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonyl-imidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

199. 1-(2-Butyloxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonyl-imidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

200. 1-(3-Pentyloxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonyl-imidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

201. 1-(1-Butyloxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonyl-imidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

202. 4-Heptyloxycarbonyloxymethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonyl-imidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

203. 1-(4-Heptyloxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonyl-imidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

204. 1-(1-Pentyloxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonyl-imidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

205. 1-(4-Methyl-1-pentyloxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

206. 5-Nonyloxycarbonyloxymethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonyl-imidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

207. 1-(5-Nonyloxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonyl-imidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

208. 1-(2,2-Dimethyl-1-propyloxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

209. 1-(3,3-Dimethyl-2-butyloxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

210. Cyclohexylmethoxycarbonyloxymethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfoniylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

211. 1-(Cyclohexylmethoxycarbonyloxy)-1-propyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

212. 1-(Dicyclohexylmethoxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

213. Cyclohexyloxycarbonyloxymethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonyl-imidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

214. 1-(Cyclohexyloxycarbonyloxy)-2-methyl-1-propyl (1S,5R,6S)-6-((1R)-1-hyoroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

215. Cyclohexyl(cyclohexyloxycarbonyloxy)methyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulifonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

216. (1R,2S,5R)-(l)-menthyloxycarbonyloxymethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

217. 1-((1R,2S,5R)-(1)-Menthyloxycarbonyloxy)-ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

218. (1S,2R,5S)-(d)-Menthyloxycarbonyloxymethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

219. (1S,2R,5R)-isomenthyloxycarbpnyloxymethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

220. (1S,2S,5R)-Neomenthyloxycarbonyloxymethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

221. 3,3,5,5-Tetramethylcyclohexyloxycarbonyloxy-methyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

222. 2-Adamantyloxycarbonyloxymethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonyl-imidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

›DETAILED DESCRIPTION OF THE INVENTION · 12 of 17

223. 1-((Indan-2-yl)oxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

224. 1-(2-Methylphenoxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

225. 1-(2-Ethylphenoxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

226. 1-(3-Methylphenoxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

227. 1-(4-Methylphenoxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

228. 1-(2,6-Dimethylphenoxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

229. 1-(2,4-Dimethylphenoxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

230. 1-(3,5-Dimethylphenoxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

231. 1-(2,4,6-Trimethylphenoxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulilfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

232. 1-(4-t-Butylphenoxycarbonyloxy)ethyl-(1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

233. (Indan-5-yl)oxycarbonyloxymethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

234. 1-((Indan-5-yl)oxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimildazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

235. 1-((Indan-5-yl)oxycarbonyloxy)-1-propyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

236. Ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

237. 2-Propyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

238. 1-Decyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

239. (Z)-2-(3-Phthalidylidene)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonyl-imidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

240. Acetoxymethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo-[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

241. 1-(Acetoxy)ethyl (1S,5R,6S)-6-((R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo-[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

242. 1-(Isobutyryloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo-[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

243. Pivaloyloxymethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo-[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

244. 1-(Pivaloyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo-[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

245. 2-Ethylbutyryloxymethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo-[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

246. 1-(2-Ethylbutyryloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

247. Cyclohexylcarbonyloxymethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

248. 1-(Cyclohexylcarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxethyl)-1-methyl-2-(7-methylthio-imidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

249. Dicyclohexylacetoxymethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthio-imidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

250. 1-Adamantylcarbonyloxymethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthio-imidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

251. 1-(1-Adamantylcarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthio-imidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxlate (a mixture of diastereomers)

252. 3-Phthalidyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo-[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

253. Benzoyloxymethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo-[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

254. 1-(Benzoyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo-[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

255. 2-Methylbenzoyloxymethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo-[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carbolxylate

256. 1-(2-Methylbenzoyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthio-imidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture diastereomers)

257. 4-Methylbenzoyloxymethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo-[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

258. 4-(2-Propyl)benzoyloxymethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthio-imidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

›DETAILED DESCRIPTION OF THE INVENTION · 13 of 17

259. 2,4-Dimethylbenzoyloxymethyl (1S,5R,6S)-6-(1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthio-imidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

260. 2,4,6-Trimethylbenzoyloxymethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthio-imidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

261. 1-(Benzyloxyacetoxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthio-imidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

262. 1-(Ethoxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthio-imidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carbokylate (a mixture of diastereomers)

263. 2-Propyloxycarbonyloxymethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthio-imidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

264. 1-(2-Propyloxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthio-imidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

265. 1-(1-Propyloxycarbonyloxy)-1-propyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthiimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxyiate (a mixture of diastereomers)

266. 2-Methyl-1-(2-propyloxycarbonyloxy)-1-propyl

(1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

267. 1-1-Propyloxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthio-imidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

268. 3-Pentyloxycarbonyloxymethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

269. 1-(3-Pentyloxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthio-imidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carbolxylate (a mixture of diastereomers)

270. 1-(1-Butyloxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthiolimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

271. 4-Heptyloxycarbonyloxymethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

272. 1-(4-Heptyloxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthio iniidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

273. 1-(3-Methyl-1-butyloxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

274. 1-(1-Pentyloxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthio-imidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

275. 1-(4-Methyl-1-pentyloxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

276. 5-Nonyloxycarbonyloxymethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthio-imidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

277. 1-[3-(2,4-Dimethyl)pentoxycarbonyloxy]ethyl (1S,5R,6S)-6-((R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

278. 1-(2,2-Dimethyl-1-propyloxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

279. 1-(33-Dimethyl-2-butyloxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

280. 1-(2-Cyclohexyl-1-ethyloxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

281. 1-(2-Phenyl-1-ethyloxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-metlhylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

282. Cyclohexyloxycarbonyloxymethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

283. 1-(Cyclohexyloxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

284. 1-(Cyclohexyloxycarbonyloxy)-1-propyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

285. 1-(Cyclohexyloxycarbonyloxy)-2-methyl-1-propyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

286. Cyclohexyl(cyclohexyloxycarbonyloxy)methyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

287. 2-Adamantyloxycarbonyloxymethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

288. Phenoxycarbonyloxymethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo-[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

289. 1-(Phenoxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthio-imidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

290. 1-(Phenoxycarbonyloxy)-1-propyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthio-imidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

291. 1-(2-Methylphenoxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

292. 1-(2-Ethylphenoxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

›DETAILED DESCRIPTION OF THE INVENTION · 14 of 17

293. 1-(2-Methoxyphenoxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

294. 1-(3-Methylphenoxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

295. 1-(3-Methoxyphenoxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-((7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

296. 1-(4-Methylphenoxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

297. 1-(4-Ethylphenoxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

298. 1-(4-Methoxyphenoxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxy late (a mixture of diastereomers)

299. 1-(2,6-Dimethylphenoxycarbonyloxy)ethyl (1S,5R,6R)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

300. 1-(2,4-Dimethylphenoxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

301. 1-(2,5-Dimethylphenoxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

302. 1-[2-Methyl-5-(2-propyl)phenoxycarbonyl]-ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

303. 1-(3,5-Dimethylphenoxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

304. 1-(2,4,6-Trimethylphenoxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

305. 1-((Indan-5-yl)oxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers) (a mixture of diastereomers)

306. 1-((Indan-5-yl)oxycarbonyloxy)-1-propyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

307. 1-Heptyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

308. 5-Methyl-2-oxo-1,3-dioxolen-4-ylmethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

309. (Z)-2-(3-Phthalidylidene)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthio-imidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

310. 1-(1,1-Dimethyl-1-butyloxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

311. 1-(3,3-Dimethyl-1-butyloxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

312. 1-(2-Methoxybenzoyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthio-imidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

313. 3,5-Dimethylbenzoyloxymethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthio-imidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

314. 1-[2-(2-Propyl)phenoxycarbonyloxy]ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

315. (2,2-Dimethyl-1-propyloxycarbonyloxy)methyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

316. 1-2-Ethyl-1-butyloxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-ethyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

317. 1-(3-Methyl-1-butyloxycarbonyloxy)-1-propyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

318. 1-(2,6-Dimethylphenoxycarbonyloxy)methyl 1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

319. 1-(2,3,5-Trimethylphenoxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

320. 2-Naphthylcarbonyloxymethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthio-imidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

321. 2,5-Dimethylbenzoyloxymethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthio-imidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

322. Cyclohexyloxycarbonyloxymethyl (1S,5R,6S)-2-[7-(N,N-dimethylaminosulfonyl)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

323. 2-Methyl-1-(phenoxycarbonyloxy)-1-propyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

324. 1-(1-Naphthoxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

325. 1-[2-(1-Propyl)phenoxycarbonyloxy]ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

326. (2-Ethylphenoxycarbonyloxy)ethyl (1S,5R,6S)-2-(7-etylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

›DETAILED DESCRIPTION OF THE INVENTION · 15 of 17

327. (2-Ethylphenoxycarbonyloxy)ethyl (1S,5R,6S)-2-[7-(N,N-dimethylaminosulfonyl)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

328. Pivaloyloxymethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylsulfinyl-imidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

329. 1-1-(2-Benzyloxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

330. 1-(2-Methyl-1-propyloxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

331. 4-(N,N-di-n-propylaminosulfonyl)benzoyl-oxymethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

332. 11-[4-(N,N-Di-n-propylaminosulfonyl)benzoyl-oxy]ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers).

Preparation of the Compounds

The compounds according to the present invention can be prepared by a variety of methods. The preferred preparation methods are shown below.

Process (1)

The compound of the formula (I) in which R is hydrogen can be prepared according to the following reaction scheme.

wherein

R 1 , R 2 , R 3 , R 4 and R 5 have the same meaning as defined in the formula (I), R 6 represents hydrogen or a hydroxyl protecting group such as t-butyldimethylsilyl, trimethylsilyl, triethylsilyl, 4-nitrobenzyloxycarbonyl, 4-methoxybenzyloxycarbonyl, R 7 represents a carboxyl protecting group such as 4-nitrobenzyl, 4-methoxybenzyl, diphenylmethyl, t-butyldimethylsilyl,

R 8 represents lower alkyl, preferably n-butyl and methyl,

R 9 , R 10 , R 11 , and R 12 have the same meaning as R 1 , R 2 , R 3 , R 4 and R 5 or represent a protected group thereof in which a functional group such as hydroxy, amino, carboxy, and hydroxyimino is protected by a conventional protective group.

The compound of the formula (II) can be prepared by the ordinary method, and the tin compound of the formula (IV) can be prepared by a method described below.

In the first step, the compound of the formula (II) can be converted into the compound of the formula (III) by the following method. The compound (III) can be prepared by reacting the compound of the formula (II) with one (1) equivalent or an excessive amount of anhydrous trifluoromethanesulfonic acid in the presence of an organic base, preferably diisopropylethylamine in an amount of one (1) equivalent or an excessive amount to anhydrous trifluoromethanesulfonic acid in an inert solvent such as acetonitrile, tetrahydrofuran, dichloromethane, and toluene, and the mixed solvent thereof at a temperature of −50° C.-+50° C. for 10 minutes-24 hours, and then subjecting the reaction mixture to the usual purification procedure.

In the second step, the compound of the formula (III) can be converted into the compound of the formula (V) by the following method. The compound of the formula (V) can be prepared by reacting the compound of the formula (III) with one (1) equivalent or an excessive amount of the compound of the formula (V) in the presence of 0.001-1 equivalent of a palladium catalyst such as tetrakis(triphenylphosphine)palladium(0), tris(dibenzylideneacetone)-dipalladium(0) or tris(dibenzylideneacetone)dipalladium(0)-chloroform adduct, 0.01-1 equivalent of a phosphine ligand such as triphenylphosphine, tri-2-furylphosphine, or tri-2-thienylphosphine, tris(2′,4,6-trimethoxyphenyl)phosphine, and 1-10 equivalents of an additive such as zinc chloride, lithium chloride, or cesium fluoride alone or in combination thereof in an inert solvent such as tetrahydrofuran, dimethoxyethane, dioxane, acetonitrile, acetone, ethanol, dimethylsulfoxide, sulfolane, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidinone, or hexamethylphosphoric triamide, or a mixed solvent thereof at 0° C.-100° C. for 10 minutes-7 days, and then, subjecting the reaction mixture to the ordinary post-treatment.

In the third step, the protective groups R 6 and R 7 or the protective groups on R 9 , R 10 , R 11 , and R 12 in the compound of the formula (V) can be removed by the deprotection reaction in one step or plural steps depending on the kinds of the protective groups to obtain the compound of the formula (I) according to the present invention. The deprotection reactions, which depend on the kinds of the protective groups R 6 and R 7 or the protective groups on R 9 , R 10 , R 11 , and R 12 used, can be carried out according to the usual methods generally known in the art. When either one or both of the protective groups can be removed under the acidic condition, a mineral acid such as hydrochloric acid, an organic acid such as oxalic acid, acetic acid or citric acid, or a Lewis acid such as aluminium chloride is used. When the protective groups is removed under a reducing condition, catalytic reduction with a variety of catalysts, or a metallic reducing agent such as zinc or iron is used. When R 6 is a silyl type protective group such as a t-butyldimethylsilyl group, a trimethylsilyl group or a triethylsilyl group, it can be easily removed with use of a fluorine ion reagent such as tetrabutylammonium fluoride. When R 6 is an allyloxycarbonyl group and R 7 is an allyl group, the protective groups can be easily removed with use of a variety of palladium complexes such as tetrakis(triphenylphosphine)palladium(0).

Process (2)

The compound of the formula (V) in which at least one of R 9 , R 10 , R 11 , and R 12 is lower alkylthio can be converted to the compound of formula (V′) in which the lower alkylthio group is converted to lower alkylsulfonyl or lower alkylsulfinyl according to the following reaction.

in which

R 1 has the same meaning as defined in the formula (I),

R 6 , R 7 , R 9 , R 10 , R 11 and R 12 have the same meaning as defined in the formula (V) in Process (1) above, R 13 , R 14 , R 15 and R 16 have the same meaning as R 9 , R 10 , R 11 and R 12 , provided that at least one of R 9 , R 10 , R 11 and R 12 represents lower alkylthio and at least one of R 13 , R 14 , R 15 and R 16 represents lower alkylsulfonyl or lower alkylsulfinyl.

›DETAILED DESCRIPTION OF THE INVENTION · 16 of 17

The compound of the formula (V) can be converted into the compound of the formula (V′) by reacting the compound of the formula (V) with one (1) equivalent or an excessive amount of an oxygenation agent (e.g. OXONE by Du Pont, m-chloroperbenzoic acid) in an inert solvent such as THF, dioxane, dichloromethane, chloroform or water or a mixed solvent thereof at a temperature of −50° C.-+100° C. for 10 minutes-7 days, and then subjecting the reaction mixture to the usual purification procedure.

The compound of the formula (V′) can be concerted to the compound of the formula (I) in the same manner as in the third step of Process (1).

The compound of the formula (I) thus obtained can be isolated and purified by crystallization or by chromatography with a nonionic macro-high porous resin, gel filtration with Sephadex or the like, or reverse phase silica gel column chromatography.

Process (3)

The compounds of the formula (I) in which R represents an ester hydrolizable in organisms can be prepared by converting the compounds represented by the formula (I) in which R is hydrogen into the ester derivatives.

in which

R 1 , R 2 , R 3 , R 4 , and R 5 have the same meanings as defined in the formula (I),

R 17 represents C 1-10 alkyl,

arylcarbonyloxy-lower alkyl group, aryl lower alkyloxy-lower-alkylcarbonyloxy-lower alkyl group, lower alkylcarbonyloxy-lower-alkyl, lower cycloalkylcarbonyloxy-lower alkyl, lower cycloalkyl-lower-alkylcarbonyloxy-lower-alkyl, dicyclohexylmethylcarbonyloxy-lower-alkyl, adamantylcarbonyloxy-lower-alkyl, lower alkyloxycarbonyloxy-lower-alkyl, lower cycloalkyloxycarbonyloxy-lower-alkyl, (lower cycloalkyloxycarbonyloxy)(lower-cycloalkyl)methyl, lower cycloalkyl-lower-alkyloxycarbonyloxy-lower-alkyl, adamantyloxlycarbonyloxy-lower-alkyl, 2-indanyloxycarbonyloxy-lower-alkyl in which the aromatic ring may be substituted, aryl-lower-alkyloxycarbonyloxy-lower-alkyl, aryloxycarbonyloxy-lower-alkyl in which the aromatic ring may be substituted, 5-indanyloxycarbonyloxoy-lower-alkyl in which the aromatic ring may be substituted, 2-oxo-5-lower alkyl-1,3-dioxolen-4-ylmethyl, 3-phthalidyl in which the aromatic ring may be substituted, or 2-(3-phthalidylidene)ethyl in which the aromatic ring may be substituted, X represents a leaving group such as Cl, Br, I, —OSO 2 CF 3 , —OSO 2 CH 3 , or —OSO 2 PhCH 3 .

The compound of the formula (I′) can be prepared by reacting the compound of the formula (I) with an alkyl halide R 17 —X in the presence of one (1) equivalent or an excessive amount of a base at a temperature of −70-+50° C., preferably −30° C.-+20° C. for 10 minutes 24 hours.

The base usable in the reaction includes for example organic bases such as diisopropylethylamine, diazabicyclo[2,2,2]undecene and 2,6-lutidine, and inorganic bases such as sodium hydroxide, potassium hydroxide, sodium hydrogen carbonate, potassium hydrogen carbonate, sodium carbonate, potassium carbonate and cesium carbonate.

The alkyl halide R 17 —X includes for example

pivaloyloxymethyl iodide,

1-(pivaloyloxy)ethyl iodide,

isobutyryloxymethyl iodide,

1-(isobutyryloxy)ethyl iodide,

acetoxymethyl iodide,

1-(acetoxy)ethyl iodide,

(1-methyl cyclohexan-1-yl)carbonyloxymethyl iodide,

benzoyloxymethyl iodide,

1-(benzoyloxy)ethyl iodide,

1-(2-methylbenzoyloxy)ethyl iodide,

4-t-butylbenzoyloxymethy iodide,

2,4,6-trimethylbenzoyloxymethyl iodide,

4-(N,N-di-n-propylaminosulfonyl)benzoyloxymethyl iodide,

1-[4-(N,N-di-n-propylaminosulfonyl)benzoyloxy]ethyl iodide,

2-naphtylcarbonyloxymethyl iodide,

1-adamantylcarbonyloxymethyl iodide,

1-(1-adamantylcarbonyloxy)ethyl iodide,

cyclohexyloxycarbonyloxymethyl iodide,

1-(cyclohexyloxycarbonyloxy)ethyl iodide,

1-(cyclohexyloxycarbonyloxy)-1-propyl iodide,

1-[(cyclohexylmethoxy)carbonyloxy]ethyl iodide,

1-[(cyclohexylethoxy)carbonyloxy]ethyl iodide,

1-(ethoxycarbonyloxy)ethyl iodide,

1-[(2-methylcyclohexan-1-yl)oxycarbonyloxy]ethyl iodide,

cyclopentyloxycarbonyloxymethyl iodide,

1-(isopropyloxycarbonyloxy)ethyl iodide,

(1R,2S,5R)-(1)-menthyloxycarbonyloxymethyl iodide,

(1S,2R,5S)-(d)-menthyloxycarbonyloxymethyl iodide,

2-adamantyloxycarbonyloxymethyl iodide,

1-(2-phenyl-1-ethyloxycarbonyloxy)ethyl iodide,

phenyloxycarbonyloxymethyl iodide,

1-(phenyloxycarbonyloxy)ethyl iodide,

1-(4-methylphenoxycarbonyloxy)ethyl iodide,

1-(2-methylphenoxycarbonyloxy)ethyl iodide,

1-(2-ethylphenoxycarbonyloxy)ethyl iodide,

1-[2-(2-propyl)phenoxycarobonyloxy]ethyl iodide,

1-(2,4-dimethylphenoxycarobonyloxy)ethyl iodide,

1-(2,5-dimethylphenoxycarbonyloxy)ethyl iodide,

1-(3,5-dimethylphenoxycarbonyloxy)ethyl iodide,

1-(2,3,5-trimethylphenoxycarbonyloxy)ethyl iodide,

1-(2,6-dimethylphenoxycarbonyloxy)methyl iodide,

2-methyl-1-(phenoxycarbonyloxy)-1-propyl iodide,

1-(2-methoxyphenoxycarbonyloxy)ethyl iodide,

1-(1-naphthoxycarbonyloxy)ethyl iodide,

1-(indan-5-yl)oxycarbonyloxymethyl iodide,

1-((indan-5-yl)oxycarbonyloxy)methyl iodide,

1-((indan-5-yl)oxycarbonyloxy)-1-propyl iodide,

(5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl bromide,

3-phthalidyl bromide,

4-(Z)-2-(3-phthalidylidne)ethyl bromide.

The inert solvent usable in the reaction includes N,N-dimethylforamide, N,N-dimethylacetamide N,N-diethylformamide, N,N-diethylacetamide, N-methylpyrrolidinone, N,N-dimethylimidazolidinoen, dimethylsulifoxide, sulfolane, acetonitrile, acetone, ethyl acetate, tetrahydrofuran, 1,4-dioxane, diethyl ether, anisole, dichloromethane, 1,2-dichloroethane, chloroform, toluene, benzene, hexamethylphosphoric triamide, methanol, and ethanol.

The compound (I′) thus obtained can be isolated and purified by precipitation, crystallization, gel filtration with Sephadex, or silica gel chromatography.

Process (4)

The compound of the formula (IV) used in the above described reaction can be prepared by the following method.

in which

R 9 , R 10 , R 11 , and R 12 , either one of which is M or R 8 3 SN, and the remaining three, which may be the same or different, have the same meanings as R 2 , R 3 , R 4 , and R 5 or represent a protected group thereof in which a functional group such as hydroxyl, amino, carboxy, and hydroxyimino is protected by a conventional protective group,

›DETAILED DESCRIPTION OF THE INVENTION · 17 of 17

R 8 represents lower alkyl, preferably n-butyl or methyl,

M represents Li, MgCl, MgBr or MgI, and

Z represents Cl, Br, I or —OSO 2 CF 3 .

The compound of the formula (VI) used can be prepared according to the method described in WO98/023623.

The compound of the formula (VI) can be converted into the compound of the formula (IV) by the following method. The compound of the formula (IV) can be prepared by reacting the compound of the formula (VI) in an inert solvent such as tetrahydrofuran, diethyl ether, 1,4-dioxane, anisole, dimethoxyethane, dichloromethane or toluene solely or in combination thereof with R 8 3 SNZ in a proportion of one (1) equivalent or an excessive amount to the compound of the formula (VI) at a temperature of −100° C.-+50° C. for 15 minutes-24 hours, and then subjected to the usual post-treatment.

The compound of the formula (IV) thus obtained can be isolated and purified by crystallization or by chromatography with a nonionic macro-high porous resin, gel filtration with Sephadex, or the like, or reverse phase silica gel column chromatography.

Use of the Compound/pharmaceutical Composition

The compound according to the present invention has wide and strong anti-microbial activities against Gram-positive and Gram-negative bacteria, and exhibits strong anti-microbial activities against MRSA, PRSP, enterococci, influenza and β-lactamase producing bacteria as well. Furthermore, it has low toxicity and stable to DHP-1. Thus, the compound according to the present invention can be used for the treatment of infections caused by various pathogenic bacteria in animals including human

The compound of the formula (I) in which R represents a group hydrolyzable in organisms above all can be advantageously administered orally because of its excellent oral absorption property.

The pharmaceutical composition comprising the compound according to the present invention and a pharmacologically acceptable salt and ester thereof as an effective ingredient can be adminitered orally or parenterally by the adminitration routes including intravenous injection, intramuscular injection, or subcutaneous, rectal or percutaneous administration to human beins and the other animals. Thus, the pharmaceutical composition comprising the compound according to the present invention as an effective ingredient can be formed into appropriate dosage forms depending on its administration routes, and specifically prepared primarily into any one of the preparation forms including injections such as intravenous injection and intramuscular injection, preparations for oral administration such as capsules, tablets, granules, powder, pills, particulates, troches, preparations for rectal administration, and fatty suppositories. These preparations can be prepared by the usual methods with ordinarily used excipients, fillers, binding agents, humidifiers, disintegrants, surface active agents, lubricants, dispersants, buffers, storing agents, dissolution aids, preservatives, flavoring agents, analgesic agents, stabilizing agents, and the like. Such non-toxic additives which can be used include for example lactose, fructose, glucose, starch, gelatin, magnesium carbonate, synthetic magnesium silicate, talc, magnesium stearate, methylcellulose or a salt thereof, gum arabic, polyethylene glycol, syrup, petrolatum, glycerol, ethanol, propylene glycol, citric acid sodium chloride, sodium sulfite, sodium phosphate, and the like. The dosage amount is appropriately determined in consideration of the dosage route, and the age, sex and condition of a patient, and the preparation may be administered for the treatment of infections usually in an amount of about 25 mg-2000 mg, preferably 50 mg-1000 mg per day for adult in one or several portions.

›EXAMPLES · 1 of 19

The following examples and Preparations further illustrate the present invention but are not intended to limit it.

Preparation 1

7-Propionyl-3-(tri-n-butylstannyl)imidazo[5,1-b]thiazole and 7-Propionyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

a) 7-Propionylimidazo[5,1-b]thiazole

Aluminum chloride (16.0 g) was added to a solution of 12.1 ml of propionyl chloride in 100 ml of carbon disulfide. A solution of 2.48 g of imidazo[5,1-b]thiazole in 100 ml of dichloromethane was added dropwise thereto. The mixture was stirred at room temperature for 18 hr. Propionyl chloride (12.1 ml) and 16.0 g of aluminum chloride were further added thereto, followed by stirring for 24 hr. The reaction solution was poured into 100 g of ice. Dichloromethane (200 ml) was added thereto. Sodium carbonate (100 g) and sodium sulfate (100 g) were added in that order to the mixture with stirring. The insolubles were removed by filtration and washed with dichloromethane. The filtrate was concentrated under the reduced pressure. Ethyl acetate (10 ml) was added to the concentrate. The crystals thus formed were collected by filtration. The filtrate was purified by column chromatography on silica gel (dichloromethane:ethyl acetate=1:1), and then combined with the collected crystals to obtain 2.49 g of 7-propionylimidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 1.26 (3H, t, J=7.4 Hz), 3.07 (2H, q, J=7.4 Hz), 7.10 (1H, d, J=4.2 Hz), 7.54 (1H, d, J=4.2 Hz), 8.00 (1H, s).

b) 7-Propionyl-3-(tri-n-butylstannyl)imidazo[5.1-b]thiazole and 7-Propionyl-2-tri-1-butylstannyl)imidazo[5,1-b]thiazole

A 1.0 N lithiumbis(trimethylsilyl)amide/THF solution (6.17 ml) was added to 60 ml of THF. A solution of 2.12 ml of tri-n-butylstannyl chloride in 24 ml of THF and a solution of 1.11 g of 7-propionylimidazo[5,1-b]thiazole in 24 ml of THF were dropwise added in that order in an argon atmosphere at −73° C. to the mixture. The mixture was stirred at the same temperature for one hr. A 1.0 N lithiumbis(trimethylsilyl)amide/THF solution (6.17 ml) was added dropwise thereto. The mixture was stirred at the same temperature for 2 hr. An ammonium chloride solution (250 ml) was added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, and filtered. The solvent was removed by distillation under the reduced pressure. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=2:1). Of two main components, the fraction, which had been eluted earlier, was collected to give 234 mg of 7-propionyl-3-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 0.91 (9H, m), 1.30 (15H, m), 1.60 (6H, m), 3.07 (2H, q, J=7.4 Hz), 6.88 (1H, s), 7.88 (1H, s).

Of the two main components, the fraction, which had been eluted later, was collected to give 234 mg of 7-propionyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 0.91 (9H, t, J=7.1 Hz), 1.18 (6H, m), 1.261(3H, t, J=7.4 Hz), 1.35 (6H, m), 3.05 (2H, q, J=7.4 Hz), 7.27 (1H, s), 7.93 (1H, s).

Preparation 2

7-(4-Nitrobenzyloximinoethyl)-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole (a Geometrical Isomer Derived From a Starting Compound as a Low-polarity Oxime Isomer)

a) 7-Formylimidazo[5,1-b]thiazole

DMF (15.48 ml) was added to 80 ml of dichloromethane. A solution of 18.32 ml of phosphorus oxychloride in 80 ml of dichloromethane was dropwise added thereto under ice cooling. A reaction was allowed to proceed at room temperature for 30 min. A solution of imidazo[5,1-b]thiazole in 40 ml of dichloromethane was added dropwise thereto. The mixture was heated under reflux for 2.5 hr. The reaction solution was poured into ice. The reaction solution was adjusted to pH 9.8 by the addition of a 5 N aqueous sodium hydroxide solution, followed by extraction five times with 200 ml of dichloromethane. The extract was dried over anhydrous magnesium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by column chromatography on silica gel (eluting with dichloromethane:ethyl acetate=5:1, ethyl acetate alone, and then dichloromethane:methanol=10:1) to give 2.37 g of 7-formylimidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 7.17 (1H, d, J=4.1 Hz), 7.60 (1H, d, J=4.1 Hz), 8.07 (1H, s), 9.93 (1H, s).

b) 7-Hydroxyiminomethylimidazo[5,1-b]thiazole (a Low-polarity Geometrical Isomer)

7-Formylimidazo[5,1-b]thiazole (249 mg) was suspended in 10 ml of ethanol. Hydroxylamine hydrochloride (137 mg) and 2.0 ml of a 1 N aqueous sodium hydroxide solution were added under ice cooling to the suspension. The mixture was stirred at the same temperature for 1.5 hr, and then stirred at room temperature for 3 hr. The reaction solution was concentrated under the reduced pressure until the volume of the reaction solution was reduced to approximately the half of the original volume. The concentrate was adjusted to pH 12 by the addition of a potassium carbonate solution, followed by extraction three times with dichloromethane. The extract was dried over anhydrous magnesium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by column chromatography on silica gel (dichloromethane:ethyl acetate=1:2). Of two main components, the fraction, which had been eluted earlier, was collected to give 160 mg of 7-hydroxyiminomethylimidazo[5,1-b]thiazole (a low-polarity geometrical isomer).

NMR (DMSO-d 6 ) δ: 7.40 (1H, d, J=4.1 Hz), 7.98 (1H, d, J=4.1 Hz), 8.09 (1H, s), 8.27 (1H, s).

c) 7-Hydroxyiminomethyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole (a Geometrical Isomer Derived From a Starting Compound as a Low-polarity Oxime Isomer)

7-Hydroxyiminomethylimidazo[5,1-b]thiazole (a low-polarity geometrical isomer) (831 mg) was dissolved in 25 ml of THF and 5 ml of hexamethylphosphoramide (HMPA). A 1.55 N n-butyllithium/n-hexane solution (7.67 ml) was dropwise added in an argon atmosphere at −70° C. to the solution. The mixture was stirred at the same temperature for 40 min. Tri-n-butylstannyl chloride (1.84 ml) was added thereto. The mixture was stirred for 1.5 hr while raising the temperature to −40° C. An ammonium chloride solution was a added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, and filtered. The solvent was removed by distillation under the reduced pressure. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=3:1 to 1:1) to give 680 mg of 7-hydroxyiminomethyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole (a geometrical isomer derived from a starting compound as a low-polarity oxime isomer).

›EXAMPLES · 2 of 19

NMR (CDCl 3 ) δ: 0.91 (9H, t, J=4 Hz), 1.17 (6H, m), 1.35 (6H, m), 1.58 (6H, m), 7.23 (1H, s), 7.98 (1H, s), 8.30 (1H, s).

d) 7-(4-Nitrobenzyloxyiminomethyl)-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole (a Geometrical Isomer Derived From a Starting Compound as a Low-polarity Oxime Isomer)

4-Nitrobenzyl bromide (671 mg) and 290 mg of t-butoxypotassium were added in an argon atmosphere to a solution of 1.18 g of 7-hydroxyiminomethyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole (a geometrical isomer derived from a starting compound as a low-polarity oxime isomer) in 25 ml of DMF at −40° C. The mixture was stirred at the same temperature for one hr. Ethyl acetate was added to the reaction solution. The mixture was washed three times with brine, and dried over anhydrous magnesium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by column chromatography on silica gel (dichloromethane:ethyl acetate=5:1) to give 169 mg of the title compound.

NMR (CDCl 3 ) δ: 0.92 (9H, m), 1.17 (6H, m), 1.35 (6H, m), 1.59 (6H, m), 5.27 (2H, s), 7.21 (1H, s), 7.60 (2H, d, J=8.9 Hz), 7.96 (1H, s), 8.22 (2H, d, J=8.9 Hz), 8.32 (1H, s).

Preparation 3

7-Methoxyiminomethyl-3-(tri-n-butylstannyl)imidazo[5,1b]thiazole (a Stereoisomer Derived From a Starting Compound as a Low-polarity Oxime Isomer)

a) 7-Methoxyiminomethylimidazo[5,1-b]thiazole (a Low-polarity Stereoisomer)

7-Formylimidazo[5,1-b]thiazole (249 mg) was suspended in 10 ml of ethanol. o-Methylhydroxyamine hydrochloride (219 mg) and 2.67 ml of a 1 N aqueous sodium hydroxide solution were added to the suspension. The mixture was stirred at room temperature for 20 hr. The reaction solution was concentrated. Water (50 ml) was added to the concentrate, followed by extraction with dichloromethane. The extract was dried over anhydrous magnesium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by column chromatography on silica gel (dichloromethane:ethyl acetate=1:1). Of two main components, the fraction, which had been eluted earlier, was collected to give 164 mg of 7-methoxyiminomethylimidazo[5,1-b]thiazole (a low-polarity geometrical isomer).

NMR (CDCl 3 ) δ: 3.96 (3H, s), 7.01 (1H, d, J=4.1 Hz), 7.48 (1H, d, J=4.1 Hz), 8.02 (1H, s), 8.24 (1H, s)

b) 7-Methoxyiminomethyl-3-(tri-n-butylstannyl)-imidazo[5,1-b]thiazole (a Stereoisomer Derived From a Starting Compound as a Low-polarity Oxime Isomer)

7-Methoxyiminomethylimidazo[5,1-b]thiazole (a low-polarity geometrical isomer) (1.47 g) was dissolved in 44 ml of THF. A 1.55 N n-butyllithium/n-hexane solution (6.27 ml) was added dropwise in an argon atmosphere at −70° C. The mixture was stirred at the same temperature for one hr. Tri-n-butylstannyl chloride (2.77 ml) was added to the reaction mixture. The mixture was stirred for 2 hr while raising the temperature to −55° C. An ammonium chloride solution was added to the reaction solution. The mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, and filtered. The solvent was removed by distillation under the reduced pressure. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=5:1 to 3:1). The tile compound (1.68 g) was obtained from the fraction of Rf=0.7 (hexane:ethyl acetate=3:1).

NMR (CDCl 3 ) δ: 0.90 (9H, t, J=1.4 Hz), 1.24 (6H, m), 1.35 (6H, m), 1.55 (6H, m), 3.96 (3H, s), 6.81 (1H, s), 7.92 (1H, s), 8.25 (1H, s).

Preparation 4

7-Pivaloyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

a) 7-Pivaloylimidazo[5,1-b]thiazole

Aluminum chloride (6.0 g) was added to a solution of 6.1 ml of pivaloyl chloride in 50 ml of carbon disulfide. The mixture was stirred. A solution of 1.2 g of imidazo[5,1-b]thiazole in 20 ml of dichloromethane was added thereto, and the mixture was stirred at room temperature for 48 hr. Dichloromethane (200 ml) was added to the reaction mixture. The mixture was washed with water and a saturated aqueous sodium hydrogencarbonate solution in that order, and then dried over anhydrous magnesium sulfate. The solvent was removed by distillation. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=1:2) to give 0.92 g of 7-pivaloylimidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 1.39 (9H, s), 6.73 (1H, d, J=4.3 Hz), 7.32 (1H, d, J=4.3 Hz), 7.92 (1H, s).

b) 7-Pivaloyl-2-(tri-n-butylstannyl)imidazo[5,9-b]thiazole

A 1.6 N n-butyllithium/n-hexane solution (2.9 ml) was added to a solution of 0.92 g of 7-pivaloylimidazo[5,1-b]thiazole in 20 ml of dry THF in an argon atmosphere at −50° C. The mixture was stirred at the same temperature for 20 min. Tri-n-butylstannyl chloride (1.3 ml) was added thereto, followed by stirring for 20 min. A saturated aqueous ammonium chloride solution was added to the reaction mixture. Ethyl acetate was added thereto. The mixture was washed with water and saturated brine in that order. The organic layer was dried over anhydrous magnesium sulfate. The solvent was removed by distillation. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=1:3) to give 0.82 g of the title compound.

NMR (CDCl 3 ) δ: 0.92 (9H, t, J=7.12 Hz), 1.13 (6H, t, J=8.4 Hz), 1.30-1.40 (15H, m), 1.52-1.62 (6H, m), 7.08 (1H, s), 7.88 (1H, s).

Preparation 5

7-Acetyl-3-methyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

a) 7-Acetyl-3-methylimidazo[5,1-b]thiazole

Aluminum chloride (16.0 g) was added to a solution of 10.0 ml of acetyl chloride in 100 ml of carbon disulfide at room temperature. The mixture was stirred for 30 min. A solution of 2.76 g of 3-methylimidazo[5,1-b]thiazole in 40 ml of dichloromethane was added dropwise thereto over a period of 15 min with stirring. The mixture was further stirred for 6 hr. The reaction solution was added to a mixture of 200 ml of dichloromethane with 100 g of ice with thorough stirring. After dissolution of the ice, 40 g of sodium carbonate and 50 g of sodium sulfate were added in that order with thorough stirring. The mixture was stirred under ice cooling for 30 min. After standing, the organic layer was separated by decantation. The gum residue was extracted with dichloromethane (100 ml, five times), and then combined with the organic layer. The combined organic layer was dried over anhydrous magnesium sulfate, and concentrated to dryness under the reduced pressure. Ethyl acetate (10 ml) was added to the concentrate. The resultant solid was triturated with 10 ml of ethyl acetate, collected by filtration, and washed with a minor amount of ethyl acetate. The washed product was dried under the reduced pressure to give 2.92 g of 7-acetyl-3-methylimidazo[5,1-b]thiazole.

›EXAMPLES · 3 of 19

NMR (CDCl 3 ) δ: 2.51 (3H, d, J=1.3 Hz), 2.61 (3H, s), 7.66 (1H, q, J=1.3 Hz), 7.88 (1H, s).

b) 7-Acetyl-3-methyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

A 1.0 N lithiumbis(trimethylsilyl)amide/n-hexane solution: (2.2 ml) was added dropwise to a solution of 0.360 g of 7-acetyl-3-methylimidazo[5,1-b]thiazole in THF (20 ml) at −70° C. The mixture was stirred for 15 min. A 1.6 N n-butyllithium/n-hexane solution (2.8 ml) was added dropwise to the reaction solution at the same temperature. The mixture was stirred for one hr. A solution (4 ml) of 0.846 g of tri-n-butylstannyl chloride in THF was added dropwise to the reaction solution. The mixture was stirred at −40° C. for 30 min. The reaction solution was added under ice cooling to a mixed solution composed of ether (50 ml) and 0.2 N phosphate buffer (pH 7) (50 ml) with thorough stirring. The organic layer was separated, washed with 0.2 N phosphate buffer (pH 7) (30 ml), and dried over anhydrous magnesium sulfate. The solvent was removed by distillation. The residue was subjected to separation and purification by flash column chromatography on silica gel (ethyl acetate) to give 0.752 g of the title compound.

NMR (CDCl 3 ) δ: 9.90 (9H, t, J=7.3 Hz), 1.10 to 1.43 (12H, m), 1.50 to 1.62 (6H, m), 2.46 (3H, s), 2.60 (3H, s), 7.80 (1H, s).

Preparation 6

7-(2-Formylamino)propionyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

a) 7-Acetylimidazo[5,1-b]thiazole

In the same manner as in Preparation 9-a), 5.09 g of 7-acetylimidazo[5,1b]thiazole was obtained from 4.97 g of imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 2.62 (3H, s), 7.10 (1H, d, J=4.1 Hz), 7.55 (1H, d, J=4.1 Hz), 8.00 (1H, s); MS (TS): 167 (M + +H).

b) 7-Azidoacetylimidazo[5,1-b]thiazole

A 1.0 N lithiumbis(trimethylsilyl)amide/n-hexane solution (5.8 ml) was added to a solution of 0.83 g of 7-acetylimidazo[5,1-b]thiazole in 20 ml of dry THF and 5 ml of HMPA in an argon atmosphere at −50° C. The mixture was stirred for 30 min. Trimethylsilyl chloride (0.76 ml) was added thereto at −20° C. The mixture was stirred for 30 min. Further, a solution of 1.07 g of N-bromosuccinimide in 20 ml of dry THF was added thereto at 0° C. The mixture was stirred at room temperature for 2 hr. Ethyl acetate was added to the reaction mixture. The mixture was washed with water and saturated brine in that order, and dried over anhydrous magnesium sulfate. DMF (10 ml) was added thereto. The solvent was concentrated. Sodium azide (0.39 g) was added to a solution of the reaction mixture in 10 ml of DMF. The mixture was stirred at room temperature for 12 hr. Ethyl acetate was added to the reaction mixture. The mixture was washed with water and saturated brine in that order, and dried over anhydrous magnesium sulfate. The solvent was removed by distillation. The residue was purified by column chromatography on silica gel (ethyl acetate) to give 0.44 g of 7-azidoacetylimidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 4.62 (2H, s), 7.17 (1H, d, J=3.6 Hz), 7.60 (1H, d, J=3.6 Hz), 8.03 (1H, s).

c) 7-Formylaminoacetylimidazo[5,1-b]thiazole

A 110% hydrochloric acid/methanol solution (1 ml) and 120 mg of 10%Pd—C were added to a solution of 0.44 g of 7-azidoacetylimidazo[5,1-b]thiazole in 50 ml of methanol and 50 ml of THF. The atmosphere in the reactor was replaced with hydrogen. The system was stirred at room temperature for 2 hr. The reaction mixture was filtered. The solvent was removed by distillation. To the residue were added 10 ml of DMF, 0.39 g of 4-nitrophenyl formate, and 0.66 ml of triethylamine. The mixture was stirred at room temperature for 30 min. Dichloromethane was added to the reaction solution. The mixture was washed with water and saturated brine in that order, and then dried over anhydrous magnesium sulfate. The solvent was removed by distillation. The residue was purified by column chromatography on silica gel (dichloromethane:methanol=10:1) to give 0.24 g of 7-formylaminoacetylimidazo[5,1-b]thiazole.

NMR (DMSO-d 6 ) δ: 4.56 (2H, d, J=5.8 Hz), 7.54 (1H, d, J=5.0 Hz), 8.11 (1H, d, J=5.0 Hz), 8.15 (1H, s), 8.33 (1H, s), 8.37 (1H, s).

d) 7-(2-Formylaminopropionyl)imidazo[5,1-b]thiazole

Sodium hydride (31 mg) was added to a solution of 0.24 g of 7-formylaminoacetylimidazo[5,1-b]thiazole in 4 ml of DMF. The mixture was stirred at 60° C. for 30 min, and cooled to room temperature. Thereafter, 176 mg of methyl iodide was added thereto. The mixture was stirred for one hr. Dichloromethane was added to the reaction mixture. The mixture was washed with water and saturated brine in that order, and dried over anhydrous magnesium sulfate. The solvent was removed by distillation. The residue was purified by column chromatography on silica gel (dichloromethane:methanol=20:1) to give 0.12 g of 7-(2-formylaminopropionyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 1.61 (3H, d, J=7.0 Hz), 5.60-5.70 (1H, m), 6.85 (1H, s), 7.16 (1H, d, J=4.1 Hz), 7.60 (1H, d, J=4.1 Hz), 8.02 (1H, s), 8.27 (1H, s).

e) 7-(2-Formylamino)propionyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

In substantially the same manner as in Preparation 4-b), 96 mg of the title compound was obtained from 0.12 g of 7-(2-formylaminopropionyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 0.85-0.95 (9H, m), 1.15-1.25 (6H, m), 1.25-1.45 (2H, m), 1.50-1.65 (9H, m), 5.60-5.70 (1H, m), 6.95 (1H, s), 7.32 (1H, s), 7.95 (1H, s), 8.26 (1H, s).

Preparation 7

7-Isobutyryl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

a) 7-Isobutyrylimidazo[5,1-b]thiazole

Aluminum chloride (16.2 g) was added to a solution of 15.0 ml of isobutyryl chloride in 100 ml of carbon disulfide. A solution of 40 ml of dichloromethane in 2.50 g of imidazo[5,1-b]thiazole was added dropwise to the mixture. The mixture was stirred at room temperature for 20 hr. Dichloromethane (100 ml) was added to the reaction solution. Water (60 ml) was added dropwise thereto with stirring. The organic layer was then separated. Dichloromethane (200 ml) and 100 g of sodium carbonate were added to the aqueous layer. The mixture was stirred. The insolubles were removed by filtration, and washed with dichloromethane. The filtrate was combined with the organic layer. The combined organic layer was dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated under the reduced pressure. The residue was purified by column chromatography on silica gel (dichloromethane:ethyl acetate=1:1) to give 2.75 g of 7-isobutyrylimidazo[5,1-b]thiazole.

›EXAMPLES · 4 of 19

NMR (CDCl 3 ) δ: 1.26 (6H, d, J=6.9 Hz), 3.73 (1H, m), 7.09 (1H, d, J=4.1 Hz), 7.54 (1H, d, J=4.1 Hz), 8.00 (1H, s).

b) 7-Isobutyryl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

A 1.0 N lithiumbis(trimethylsilyl)amide/THF solution (12 ml) was added to 60 ml of THF. Tri-n-butylstannyl chloride (2.36 ml) and a solution of 1.18 g of 7-isobutyrylimidazo[5,1-b]thiazole in 1.18 ml of THF were added dropwise thereto in an argon atmosphere at −68° C. The mixture was stirred at the same temperature for one hr. Ethyl acetate (450 ml) was added to the reaction solution, and the mixture was washed with 200 ml of brine. The organic layer was dried over anhydrous magnesium sulfate, and then filtered. The solvent was removed by distillation under the reduced pressure. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=3:2) to give 1.55 g of the title compound.

NMR (CDCl 3 ) δ: 0.86 (9H, t, J=7.3 Hz), 1.13 (6H, m), 1.21 (6H, d, J=6.9 Hz), 1.30 (6H, m), 1.53 (6H, m), 3.69 (1H, m), 7.28 (1H, s), 7.92 (1H, s).

Preparation 8

7-Acetyl-3-(tri-n-butylstannyl)imidazo[5,1-b]thiazole and 7-Acetyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

In the same manner as in Example 9-b), a reaction was allowed to proceed using 10.5 g of 7-acetylimidazo[5,1-b]thiazole was used as the starting compound. Purification was carried out by column chromatography on silica gel (hexane:ethyl acetate=1:1). Of two main components, the fraction, which had been eluted earlier, was collected to give 1.36 g of 7-acetyl-3-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 0.90 (9H, t, J=7.4 Hz), 1.31 (12H, m), 1.56 (6H, m), 2.62 (3H, s), 6.90 (1H, s), 7.89 (1H, s); MS (ESI): 457 (M + +H).

Of the two main components, the fraction, which had been eluted later, was collected to give 19.5 g of 7-acetyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 0.91 (9H, t, J=7.2 Hz), 1.19 (6H, m), 1.35 (6H, m), 1.58 (6H, m), 2.61 (3H, s), 7.28 (1H, s), 7.94 (1H, s); MS (ESI): 457 (M + +H).

Preparation 9

7-Acetyl-5-methyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

a) 7-Acetyl-5-methylimidazo[5,1-b]thiazole

Aluminum chloride (6.96 g) was added to a solution of 4.33 ml of acetyl chloride in 40 ml of carbon disulfide. A solution of 1.20 g of 5-methylimidazo[5,1b]thiazole in 40 ml of dichloromethane was added dropwise thereto. The mixture was stirred at room temperature for 24 hr. The reaction solution was poured into 40 g of ice. Dichloromethane (100 ml) was added thereto. Sodium carbonate (32 g) was added to the mixture with stirring. The insolubles were removed by filtration, and washed with dichloromethane. The filtrate was concentrated under the reduced pressure. Ethyl acetate (20 ml) was added thereto. The resultant crystal was collected by filtration. The filtrate was purified by column chromatography on silica gel (dichloromethane:methanol=20:1). The purification product was combined with the above collected crystal to give 1.45 g of 7-acetyl-5-methylimidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 2.58 (3H, s), 2.65 (3H, s), 7.06 (1H, d, J=4.2 Hz), 7.37 (1H, d, J=4.2 Hz).

b) 7-Acetyl-5-methyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

A 1.0 N lithiumbis(trimethylsilyl)amide/THF solution (3.75 ml) was added dropwise to a solution of 613 mg of 7-acetyl-5-methylimidazo[5,1-b]thiazole in 34 ml of THF in an argon atmosphere at −73° C. The mixture was stirred at the same temperature for 50 min. A 1.59 N n-butyllithium/n-hexane solution (4.71 ml) was added dropwise thereto. The mixture was stirred at the same temperature for 50 min. Tri-n-butylstannyl chloride (1.16 ml) was added dropwise thereto. The mixture was further stirred at the same temperature for 40 min. An ammonium chloride solution was added to the reaction solution, followed by extraction with ethyl acetate and washing with brine. The extract was dried over anhydrous magnesium sulfate and then filtered. The solvent was removed by distillation under the reduced pressure. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=1:1) to give 1.40 g of the title compound.

NMR (CDCl 3 ) δ: 0.91 (9H, t, J=7.4 Hz), 1.18 (6H, m), 1.35 (6H, m), 1.58 (6H, m), 2.57 (3H, s), 2.64 (3H, s), 7.06 (1H, s).

Preparation 10

7-Methanesulfonyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

A 1.6 N n-butyllithium/n-hexane solution (2.8 ml) was added to a solution of 404 mg of 7-methanesulfonylimidazo[5,1-b]thiazole in 20 ml of dry THF in an argon atmosphere at −40° C. The mixture was stirred at the same temperature for 30 min. Tri-n-butylstannyl chloride (0.6 ml) was added thereto. A saturated aqueous ammonium chloride solution was added to the reaction solution. Ethyl acetate was then added thereto. The mixture was washed with water and saturated brine in that order. The organic layer was dried over anhydrous magnesium sulfate. The solvent was removed by distillation. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=2:1) to give 251 mg of the title compound.

NMR (CDCl 3 ) δ: 0.85-0.95 (9H, m), 1.25-1.33 (6H, m), 1.25-1.40 (6H, m), 1.52-1.64 (6H, m), 3.20 (3H, s), 7.26 (1H, s), 7.99 (1H, s).

Preparation 11

7-Methanesulfonyl-3-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

a) 7-Methanesulfonylimidazo[5,1-b]thiazole

In substantially the same manner as in Example 12-a), 0.94 g of 7-methanesulfonylimidazo[5,1-b]thiazole was obtained from 2.50 g of 7-iodoimidazo[5,1b]thiazole and 0.81 ml of methanesulfonyl chloride.

NMR (CDCl 3 ) δ: 3.20 (3H, s), 7.09 (1H, d, J=4.2 Hz), 7.61 (1H, d, J=4.2 Hz), 8.10 (1H, s).

b); 7-Methanesulfonyl-3-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

A 1.6 N n-butyllithium/n-hexane solution (0.7 ml) was added to a solution of 202 mg of 7-methanesulfonylimidazo[5,1-b]thiazole in 20 ml of dry THF in an argon atmosphere at −70° C. The mixture was stirred at the same temperature for 30 min. Tri-n-butylstannyl chloride (0.3 ml) was added thereto. A saturated aqueous ammonium chloride solution was added to the reaction mixture. Ethyl acetate was then added thereto. The mixture was washed with water and saturated brine in that order. The organic layer was dried over anhydrous magnesium sulfate. The solvent was removed by distillation. The residue was purified by column chromatography on silica gel (hexane:methyl acetate=2:1) to give 110 mg of the title compound.

›EXAMPLES · 5 of 19

NMR (CDCl 3 ) δ: 0.85-0.95 (9H, m) 1.25-1.40 (12H, m), 1.50-1.60 (6H, m), 3.20 (3H, s), 6.81 (1H, s), 7.95 (1H, s).

Preparation 12

7-Methylthio-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

a-1) 7-Methylthioimidazo[5,1-b]thiazole

A 1 M ethylmagnesium bromide/THF solution (1.4 ml) was added under ice cooling to a solution of 0.31 g of 7-iodoimidazo[5,1-b]thiazole in 3 ml of dry THF in an argon atmosphere. The mixture was stirred at the same temperature for one hr. Methyl methanethiolsulfonate (0.15 ml) was added thereto. The mixture was stirred at room temperature for 12 hr. A saturated aqueous ammonium chloride solution was added to the reaction solution. Ethyl acetate was added thereto. The mixture was washed with a dilute aqueous sodium thiosulfate solution and saturated brine in that order. The organic layer was dried over anhydrous magnesium sulfate. The solvent was removed by distillation. The residue was purified by column chromatography on silica gel (ethyl acetate) to give 0.15 g of 7-methylthioimidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 2.41 (3H, s), 6.86 (1H, d, J=4.2 Hz), 7.39 (1H, d, J=4.2 Hz), 8.00 (1H, s).

a-2) 7-Methylthioimidazo[5,1-b]thiazole

To 200 ml of dichloromethane cooled at 0° C., 35 ml of trichlorotitanium and 40 g of methyl methanethiolsulfonate were added and the mixture was stirred at the same temperature for 20 min. The mixture was added dropwise to 1 L of nitrobenzene containing 26 g of imidazo[5,1-b]thiazole at 5 to 10° C. and stirred at the same temperature for five hr. The reaction was stopped by adding 400 ml of 0.5N hydrochloride, followed by filtration to remove insolubles. The mixture was washed with 200 ml of dichloromethane and 200 ml of water. The organic layer was removed and the aqueous layer was washed with 800 ml of dichloromethane twice. After the pH of the aqueous layer was adjusted to 4.0, the extraction three times with dichloromethane. The organic layer was dried and the solvent was removed to give 19.8 g of 7-Methylthioimidazo[5,1-b]thiazole.

b) 7-Methylthio-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

In substantially the same manner as in Preparation 4-b), 1.50 g of the title compound was obtained from 0.79 g of 7-methylthioimidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 0.92 (9H, t, J=7.2 Hz), 1.15 (6H, t, J=8.4 Hz), 1.30-1.40 (6H, m), 1.55-1.65 (6H, m), 2.40 (3H, s), 7.13 (1H, s), 7.94 (1H, s).

Preparation 13

7-Ethanesulfonyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

a) 7-Ethanesulfonylimidazo[5,1-b]thiazole

A solution of 725 mg of 7-methanesulfonylimidazo[5,1-b]thiazole in 35 ml of THF was cooled in an argon atmosphere to −70° C. A 1 N-lithiumbis(trimethylsilyl)amide/THF solution (3.9 ml) was added dropwise thereto at the same temperature. The mixture was stirred for 30 min. Thereafter, 0.25 ml of methyl iodide was added thereto. The mixture was stirred at the same temperature for 70 min. A saturated aqueous sodium chloride solution was added thereto, followed by extraction four times with ethyl acetate. The extract was dried over anhydrous magnesium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by column chromatography on silica gel (ethyl acetate:methanol=9:1) to give 0.79 g of 7-ethanesulfonylimidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 1.34 (3H, t, J=17.4 Hz), 3.33 (2H, q, J=7.4 Hz), 7.07 (1H, d, J=4.3 Hz), 7.55 (1H, s), 8.08 (1H, s).

b) 7-Ethanesulfonyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

A solution of 669 mg of 7-ethanesulfonylimidazo[5,1-b]thiazole in 30 ml of THF was cooled to −40° C. in an argon atmosphere. A 1.6 N n-butyllithium/n-hexane solution (4.3 ml) was added dropwise thereto at the same temperature. The mixture was stirred for 15 min. Tri-n-butylstannyl chloride (0.88 ml) was added thereto, followed by stirring at the same temperature for 10 min. A saturated aqueous ammonium chloride solution was added thereto. The mixture was extracted twice with ethyl acetate. The extract was dried over anhydrous magnesium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=1:1). The title compound (1.54 g) was obtained from the fraction of Rf=0.2.

NMR (CDCl 3 ) δ: 0.92 (9H, t, J=7.1 Hz), 1.22 (6H, m), 1.38 (9H, m), 1.58 (6H, m), 3.31 (2H, q, J=7.4 Hz), 7.26 (1H, s), 8.00 (1H, s).

Preparation 14

7(N-Methylsulfamoyl)-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

a) 7-(N-Methylsulfamoyl)imidazo[5,1-b]thiazole

In substantially the same manner as in Example 25-b), 0.34 g of 7-(N-methylsulfamoyl)imidazo[5,1-b]thiazole was obtained from 0.36 g of 7-chlorosulfonylimidazo[5,1-b]thiazole and 10 ml of a 2 M methylamine/THF solution.

NMR (CDCl 3 ) δ: 2.71 (3H, d, J=5.4 Hz), 4.76-4.85 (1H, m), 7.04 (1H, d, J=4.1 Hz), 7.53 (1H, d, J=4.1 Hz), 8.06 (1H, s).

b) 7-(N-Methylsulfamoyl)-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

A 1.6 N n-butyllithium/n-hexane solution (1.6 ml) was added to a solution of 0.26 g of 7-(N-methylsulfamoyl)imidazo[5,1-b]thiazole in 8 ml of dry THF and 4 ml of HMPA in an argon atmosphere at −50° C. The mixture was stirred at the same temperature, for 30 min. Tri-n-butylstannyl chloride (0.34 ml) was added thereto. The mixture was stirred four 30 min. A 1.6 N n-butyllithium/n-hexane solution (0.8 ml) was further added thereto. The mixture was stirred for 30 min. Tri-n-butylstannyl chloride (0.2 ml) was added thereto, followed by stirring at the same temperature for 30 min. A saturated aqueous ammonium chloride solution was added thereto. Ethyl acetate was then added, followed by washing with water and saturated brine in that order. The organic layer was dried over anhydrous magnesium sulfate. The solvent was removed by distillation. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=12) to give 0.39 g of the title compound.

NMR (CDCl 3 ) δ: 0.92 (9H, t, J=7.2 Hz), 1.18 (6H, t, J=8.5 Hz), 1.30-1.40 (6H, m), 1.53-1.60 (6H, m), 2.71 (3H, d, J=5.4 Hz), 4.65-4.72 (1H, m), 7.24 (1H, s), 7.98 (1H, s).

›EXAMPLES · 6 of 19

Preparation 15

7-p-Toluenesulfonyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

a) 7-p-Toluenesulfonylimidazo[5,1-b]thiazole

A solution of 23.9 g of p-toluenesulfonyl chloride in 100 ml of dichloromethane was cooled to ice temperature in an argon atmosphere. Aluminum chloride (15.3 g) was added thereto. The mixture was stirred for 10 min. A solution of 3.15 g of imidazo[5,1-b]thiazole in 25 ml of dichloromethane was added dropwise thereto. The mixture was stirred for 22 hr. Dichloromethane (200 ml), 70 ml of water, and 75 g of a sodium carbonate powder were added thereto, followed by extraction. The extract was dried over anhydrous magnesium sulfate. The solvent was removed by distillation under the reduced pressure to give 995 mg of 7-p-toluenesulfonylimidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 2.36 (3H, s), 7.40 (2H, d, J=8.3 Hz), 7.46 (1H, d, J=4.1 Hz), 7.76 (2H, d, J=8.3 Hz), 8.03 (1H, d, J=4.1 Hz), 8.34 (1H, s).

b) 7-p-Toluenesulfonyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

A solution of: 669 mg of 7-p-toluenesulfonylimidazo[5,1-b]thiazole in 65 ml of THF was cooled to −60° C. in an argon atmosphere. A 1.6 N n-butyllithium/n-hexane solution (2.5 ml) was added dropwise thereto at the same temperature. The mixture was stirred for 20 min. A solution of 1.25 g of tri-n-butylstannyl chloride in 10 ml of THF was added thereto, and the mixture was stirred at the same temperature for 40 min. A semisaturated aqueous ammonium chloride solution (150 ml), was added thereto, followed by extraction with 250 ml of ethyl acetate. The extract was dried over anhydrous magnesium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=1:1). The title compound (590 mg) was obtained from the fraction of Rf=0.4.

NMR (CDCl 3 ) δ: 0.92 (9H, t, J=7.3 Hz), 1.83 (6H, m), 1.35 (6H, m), 1.56 (6H, m), 2.39 (3H, s), 7.20 (1H, s), 7.29 (2H, d, J=8.4 Hz), 7.91 (1H, s), 7.97 (2H, d, J=8.4 Hz).

Preparation 16

7t-Butyldimethylsilyloxyacetyl-3-(tri-n-butylstannyl)imidazo[5,1-b]thiazole and 7-t-Butyldimethylsilyloxyacetyl-2-(tri-n-butylstannyl)imidazo[5,1-b]-thiazole

a) 7-Acetoxyacetylimidazo[5,1-b]thiazole

7-Acetylimidazo[5,1-b]thiazole (2.49 g) was dissolved in a solution of 150 ml of THF and 30 ml of HMPA. A 1.0 N lithiumbis(trimethylsilyl)amide/THF solution (18 ml) was added dropwise to the solution in an argon atmosphere at −70° C. The mixture was stirred at the same temperature for 30 min. Trimethylsilyl chloride (2.28 ml) was added dropwise thereto. The mixture was stirred at the same temperature for 30 min. A solution of 3.21 g of N-bromosuccinimide in 90 ml of THF was added dropwise thereto. The mixture was stirred for 2 hr while raising the temperature to room temperature. Ethyl acetate (400 ml) was added to the reaction solution. The mixture was washed twice with brine, dried over anhydrous magnesium sulfate, and filtered. The solvent was removed by distillation under the reduced pressure. The residue was dissolved in 120 ml of DMF. Sodium acetate (1.48 g) was added to the solution. The mixture was stirred at room temperature for 14 hr and then at 60° C. for 4 hr. The reaction solution was concentrated under the reduced pressure until the amount of the solution became half. Brine (290 ml) was added to the concentrate, followed by extraction twice with 300 ml of ethyl acetate. The organic layers were combined together, washed three times with brine, dried over anhydrous magnesium sulfate, and filtered. The solvent was removed by distillation under the reduced pressure. The residue was purified by column chromatography on silica gel (eluting with dichloromethane:ethyl acetate=1:1 and then with ethyl acetate) to give 2.11 g of 7-acetoxyacetylimidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 2.24 (3H, s), 5.44 (2H, s), 7.13 (1H, d, J=4.1 Hz), 7.57 (1H, d, J=4.1 Hz), 8.00 (1H, s).

b) 7-Hydroxyacetylimidazo[5,1-b]thiazole

7-Acetoxyacetylimidazo[5,1-b]thiazole (24.6 mg) was dissolved in 2 ml of methanol and 0.5 ml of water. Potassium carbonate (17.3 mg) was added under ice cooling to the solution. The mixture was stirred for 45 min. Methanol was removed by distillation under the reduced pressure. Water (10 ml) was added to the residue, followed by extraction five times with dichloromethane. The extract was dried over anhydrous magnesium sulfate, and then filtered. The solvent was removed by distillation under the reduced pressure to give 18.8 mg of 7-hydroxyacetylimidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 3.55 (1H, t, J=14.7 Hz), 4.92 (2H, d, J=4.7 Hz), 7.16 (1H, d, J=4.1 Hz), 7.60 (1H, d, J=4.1 Hz), 8.03 (1H, s).

c) 7-t-Butyldimethylsilyloxyacetylimidazo[5,1-b]thiazole.

7-Hydroxyacetylimidazo[5,1-b]thiazole (1.42 g) was dissolved in 10 ml of DMF. Imidazole (847 mg) and 1.77 g of t-butyldimethylsilyl chloride were added to the solution in an argon atmosphere. The mixture was stirred at room temperature for 24 hr. Brine was added to the reaction solution, followed by extraction twice with ethyl acetate. The organic layers were combined together, washed with brine, dried over anhydrous magnesium sulfate, and then filtered. The solvent was removed by distillation under the reduced pressure. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=1:2) to give 2.19 g of 7-t-butyldimethylsilyloxyacetylimidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 0.16 (6H, s), 0.97 (9H, s), 5.10 (2H, s), 7.11 (1H, d, J=4.2 Hz), 7.55 (1H, d, J=4.2 Hz), 7.98 (1H, s).

d) 7-t-Butyldimethylsilyloxyacetyl-3-(tri-n-butylstannyl)imidazo[5,1-b]thiazole and 7-t-Butyldimethylsilyloxyacetyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

Tri-n-butylstannyl chloride (2.97 ml) and 16.0 ml of a 1.0 N lithiumbis(trimethylsilyl)amide/THF solution were added dropwise in that order to a solution of 2.37 g of 7-t-butyldimethylsilyloxyacetylimidazo[5,1-b]thiazole in 80 ml of THF in an argon atmosphere at −73° C. The mixture was stirred at the same temperature for 30 min. An ammonium chloride solution was added to the reaction solution, followed by extraction with ethyl acetate. The extract was dried over anhydrous magnesium sulfate, and then filtered. The solvent was removed by distillation under the reduced pressure. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate:=5:1 to 2:1). Of two main components, the fraction, which had been eluted earlier, was collected to give; 484 mg of 7-t-butyldimethylsilyloxyacetyl-3-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

›EXAMPLES · 7 of 19

NMR (CDCl 3 ) δ: 0.16 (6H, s), 0.92 (9H, t, J=7.1 Hz), 0.97 (9H, s), 1.31 (12H, m), 1.60 (6H, m), 5.10 (2H, s), 6.88 (1H, s), 7.85 (1H, s).

Of the two main components, the fraction, which had been eluted later, was collected to give 3.51 g of 7-t-butyldimethylsilyloxyacetyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 0.15 (6H, s), 0.9.1 (9H, t, J=7.2 Hz), 0.96 (9H, s), 1.18 (6H, m), 1.35 (6H, m), 1.56 (6H, m), 5.08 (2H, s), 7.27 (1H, s), 7.91 (1H, s).

Preparation 17

7-Benzoyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

a) 7-Benzoylimidazo[5,1-b]thiazole

Aluminum chloride (5.33 g) was added to a solution of 4.64 ml of benzoyl chloride in 50 ml of carbon disulfide. A solution of 1.24 g of imidazo[5,1-b]thiazole in 50 ml of dichloromethane was added dropwise thereto. The mixture was stirred at room temperature for 2 hr. The reaction solution was poured into 50 g of ice. Dichloromethane (100 ml) was added thereto. Sodium carbonate (16.7 g) and 16.7 g of sodium sulfate were added in that order to the mixture with stirring. The insolubles were removed by filtration through Celite, and then washed with dichloromethane. Filtrate was concentrated under the reduced pressure. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=5:1 to dichloromethane:ethyl acetate=2:1) to give 1.39 g of 7-benzoylimidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 7.16 (1H, d, J=4.1 Hz), 7.54 (3H, m), 7.60 (1H, d, J=4.1 Hz), 8.09 (1H, s), 8.54 (2H, m).

b) 7-Benzoyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

In the same manner as in Preparation 16-d), 2.59 g of the title compound was obtained from 1.39 g of 7-benzoylimidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 0.92 (9H, t, J=7.2 Hz), 1.21 (6H, m), 1.36 (6H, m), 1.60 (6H, m), 7.34 (1H, s), 7.53 (3H, m), 8.03 (1H, s), 8.51 (2H, m).

Preparation 18

7-(4-Nitrobenzylsulfamoyl)-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

a) 7-(4-Nitrobenzylsulfamoyl)imidazo[5,1-b]thiazole

4-Nitrobenzylamine (1.24 g) and 2 ml of diisopropylethylamine were added to a solution of 0.95 g of 7-chlorosulfonylimidazo[5,1-b]thiazole in 20 ml of DMF. The mixture was stirred at room temperature for 12 hr. Ethyl acetate was added to the reaction mixture. The mixture was washed with water and saturated brine in that order. The organic layer was dried over anhydrous magnesium sulfate. The solvent was evaporated, and the resultant powder was collected by filtration to gives 1.07 g of 7-(4-nitrobenzylsulfamoyl)imidazo[5,1-b]thiazole.

NMR (DMSO-d 6 ) δ: 4.18 (2H, s), 7.36 (1H, d, J=4.2 Hz), 7.47 (2H, d, J=12.0 Hz), 7.95 (1H, d, J=4.2 Hz), 8.07 (2H, d, J=12.0 Hz), 8.30 (1H, s), 8.44 (1H, s).

b) 7-(4-Nitrobenzylsulfamoyl)-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

A 1.0 N lithiumbis(trimethylsilyl)amide/n-hexane solution (4.8 ml) was added to a solution of 0.68 g of 7-(4-nitrobenzylsulfamoyl)imidazo[5,1-b]thiazole in 20 ml of THF and 4 ml of HMPA in an argon atmosphere at −40° C. The mixture was stirred at the same temperature for 30 min. Tri-n-butylstannyl chloride (0.57 ml) was added thereto. The mixture was stirred at the same temperature for 30 min. A saturated aqueous ammonium chloride solution was added thereto. Ethyl acetate was then added thereto. The mixture was then washed with water and saturated brine in that order. The organic layer was dried over anhydrous magnesium sulfate. The solvent was removed by distillation. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=1:1) to give 0.78 g of the tile compound.

1 NMR (CDCl 3 ) δ: 0.92 (9H, t, J=17.2 Hz), 1.19 (6H, t, J=8.4 Hz), 1:30-1.40 (6H, m), 1.55-1.65 (6H, m), 4.33 (2H, d, J=6.4 Hz), 6.25 (2H, d, J=6.4 Hz), 7.17 (1H, s), 7.49 (2H, d, J=11.0 Hz), 7.90 (1H, s), 8.07 (2H, d, J=11.0 Hz).

Preparation 19

7-Fluoro-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

a) 7-Fluoroimidazo[5,1-b]thiazole

N-Fluoro-N′-(chloromethyl)triethylenediaminebis (tetrafluoroborane) (11 g) was added to a solution of 2.0 g of imidazo[5,1-b]thiazole in 90 ml of a 1,2-dichloroethane in an argon atmosphere. The mixture was stirred at room temperature for 6 hr. A saturated aqueous sodium hydrogencarbonate solution was added thereto, followed by extraction with dichloromethane and washing with saturated brine. The extract was dried over anhydrous magnesium sulfate and then filtered. The solvent was removed by distillation under the reduced pressure. The residue was purified by column chromatography on silica gel (dichloromethane:ethyl acetate=40:1) to give 457 mg of 7-fluoroimidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 6.80 (1H, d, J=4.2 Hz), 7.32 (1H, dd, J 1 =4.2 Hz, J 2 =1.7 Hz), 7.59 (1H, s).

b) 7-Fluoro-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

A 1.0 N lithiumbis(trimethylsilyl)amide/THF solution (3.2 ml) and 0.75 ml of tri-n-butylstannyl chloride were added in that order to a solution of 7-fluoroimidazo[5,1-b]thiazole in dry THF in an argon atmosphere at −78° C. The mixture was stirred at the same temperature for 10 min. Water was added thereto, followed by extraction with ethyl acetate and washing with saturated brine. The extract was dried over anhydrous magnesium sulfate and then filtered. The solvent was removed by distillation under the reduced pressure. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=7:1) to give 820 mg of the title compound.

NMR (CDCl 3 ) δ: 0.94 (9H, t, J=7.4 Hz), 1.15 (6H, m) 1.35 (6H, m), 1.57 (6H, m), 7.04 (1H, d, J=1.7 Hz), 7.51 (1H, s).

Preparation 20

7-[N-(2-Hydroxyethyl)-N-methyl]sulfamoyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

a) 7-[N-(2-Hydroxyethyl)-N-methyl]sulfamoylimidazo[5,1-b]thiazole

In substantially the same manner as in Example 27-a), 1.11 g of 7-[N-(2-hydroxyethyl)-N-methyl]sulfamoylimidazo[5,1-b]thiazole was obtained from 1.05 g of 7-chlorosulfonylimidazo[5,1-b]thiazole and 0.46 g of N-methylethanolamine.

NMR (CDCl 3 ) δ: 2.88 (3H, s), 3.57 (2H, t, J=4.5 Hz), 3.80-3.90 (2H, m), 4.35 (1H, m), 4.30-4.40 (1H, m), 7.07 (1H, d, J=4.2 Hz), 7.55 (1H, d, J=4.2 Hz), 8.05 (1H, s).

›EXAMPLES · 8 of 19

b) 7-[N-(2-t-Butyldimethylsilyloxyethyl)-N-methyl]sulfamoylimidazo[5,1-b]thiazole

t-Butyldimethylsilyl chloride (10.33 g) and 0.16 g of imidazole were added to a solution of 0.52 g of 7-[N-(2-hydroxyethyl)-N-methyl]sulfamoylimidazo[5,1-b]thiazole in 20 ml of dichloromethane. The mixture was stirred at room temperature for 30 min. Ethyl acetate was added to the reaction mixture. The mixture was washed with water and saturated brine in that order. The organic layer was dried over anhydrous magnesium sulfate. The solvent was removed by distillation. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=1:1), to give 0.87 g of 7-[N-(2-t-butyldimethylsilyloxyethyl)-N-methyl]sulfamoylimidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 0.05 (3H, s), 0.06 (3H, s), 0.88 (9H, s), 2.99 (3H, s), 3.33 (2H, t, J=5.8 Hz), 3.84 (2H, t, J=5.8 Hz), 7.02 (1H, d, J=4.1 Hz), 7.53 (1H, d, J=4.1 Hz), 8.63 (1H, s).

c) 7-[N-(2-t-Butyldimethylsilyloxyethyl)-N-methyl]sulfamoyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

In substantially the same manner as in Preparation 4-b), 0.54 g of the title compound was obtained from 0.45 g of 7-[N-(2-t-butyldimethylsilyloxyethyl)-N-methyl]sulfamoylimidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 0.06 (6H, s), 0.85-0.95 (21H, m), 1.15-1.21 (6H, m), 1.30-1.40 (6H, m), 1.55-1.65 (6H, m), 2.99 (3H, s), 3.32 (2H, t, J=6.0 Hz), 3.83 (2H, t, J=6.0 Hz), 7.24 (1H, s), 7.96 (1H, s).

Preparation 21

7-Acetylaminoacetyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

a) 7-Acetylaminoacetylimidazo[5,1-b]thiazole

A solution (17 ml) of 10% hydrochloric acid in methanol and 800 mg of 10%Pd—C. were added to a solution of 1.78 g of 7-azidoacetylimidazo[5,1-b]thiazole in 85 ml of methanol and 85 ml of THF. The atmosphere in the reactor was replaced with hydrogen. The system was stirred at room temperature for 5 hr. The catalyst was removed by filtration through Celite and washed with methanol. The solvent was removed by distillation. The residue was dissolved in 50 ml of DMF. Pyridine (3.43 ml) and 1.22 ml of acetic anhydride were added to the solution under ice cooling. The mixture was stirred at the same temperature for 2 hr. Dichloromethane and brine were added to the reaction solution. The mixture was adjusted to pH 10 by the addition of potassium carbonate. The organic layer were separated. The aqueous layer was further extracted five times with dichloromethane. The organic layers were combined together, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under the reduced pressure. The residue was purified by column chromatography on silica gel (dichloromethane:methanol=40:1 to 20:1) to give 397 mg of 7-acetylaminoacetylimidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 2.10 (3H, s), 4.82 (2H, d, J=4.7 Hz), 6.50 (1H, br), 7.14 (1H, d, J=4.1 Hz), 7.58 (1H, d, J=4.1 Hz), 8.01 (1H, s).

b) 7-Acetylaminoacetyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

7-Acetylaminoacetylimidazo[5,1-b]thiazole (397 mg) was dissolved in 40 ml of THF and 8 ml of HMPA. Tri-n-butylstannyl chloride (0.76 ml) and 7.1 ml of a 1.0 N lithiumbis(trimethylsilyl)amide/THF solution were added dropwise in that order in an argon atmosphere at −73° C. The mixture was stirred at the same temperature for one hr. An ammonium chloride solution was added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was washed twice with brine, dried over anhydrous magnesium sulfate, and then filtered. The solvent was removed by distillation under the reduced pressure. The residue was purified by column chromatography on silica gel (eluting with ethyl acetate and then with dichloromethane:methanol=20:1) to give 152 mg of the title compound.

NMR (CDCl 3 ) δ: 0.91 (9H, t, J=7.2 Hz), 1.20 (6H, m), 1.35 (6H, m), 1.56 (6H, m), 2.09 (3H, s), 4.79 (2H, d, J=4.5 Hz), 6.58 (1H, br), 7.31 (1H, s), 7.96 (1H, s).

Preparation 22

5-Methyl-7-methylthio-3-(tri-n-butylstannyl)imidazo[5,1-b]thiazole and 5-Methyl-7-methylthio-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

a) 7-Iodo-5-methylimidazo[5,1-b]thiazole

5-Methylimidazo[5,1-b]thiazole (6.90 g) was dissolved in 500 ml of dichloromethane. N-Iodosuccinimide (10.6 g) was added to the solution. The mixture was stirred at room temperature for 24 hr. N-Iodosuccinimide (1.06 g) was added thereto, followed by stirring for additional one hr. The reaction solution was washed with an aqueous sodium thiosulfate solution and brine in that order, dried over anhydrous magnesium sulfate, and then filtered. The solvent was removed by distillation under the reduced pressure. The residue was dissolved in 200 ml of dichloromethane and 100 ml of ethyl acetate. Silica gel (30 g) was added to the solution. The mixture was stirred. The silica gel was removed by filtration. The filtrate was washed with 200 ml of a mixed solution of dichloromethane:ethyl acetate=2:1. The filtrate was concentrated under the reduced pressure to give 13.08 g of 7-iodo-5-methylimidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 2.58 (3H, s), 6.83 (1H, d, J=4.2 Hz), 7.29 (1H, d, J=4.2 Hz).

b) 5-Methyl-7-methylthioimidazo[5,1-b]thiazole

In the same manner as in Preparation 12-a), 3.56 g of 5-methyl-7-methylthioimidazo[5,1-b]thiazole was obtained from 5.28 g of 7-iodo-5-methylimidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 2.40 (3H, s), 2.56 (3H, s), 6.81 (1H, d, J=4.2 Hz), 7.20 (1H, d, J=4.2 Hz).

c) 5-Methyl-7-methylthio-3-(tri-n-butylstannyl)imidazo[5.1-b]thiazole and 5-Methyl-7-methylthio-2-(tri-n-butylstannyl)imidazo[5.1-b]thiazole

5-Methyl-7-methylthioimidazo[5,1-b]thiazole (3.34 g) was dissolved in 150 ml of THF. A 1.59 N n-butyllithium/n-hexane solution (22.8 ml) was added dropwise to the solution in an argon atmosphere at −73° C. The mixture was stirred at the same temperature for 40 min. Tri-n-butylstannyl chloride (6.39 ml) was added thereto, followed by stirring at the same temperature for one hr. An ammonium chloride solution was added to the reaction solution. The mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate, and then filtered. The solvent was removed by distillation under the reduced pressure. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=2:1 to 1:1). Of two main components, the fraction, which had been eluted earlier, was collected to give 598 mg of 5-methyl-7-methylthio-3-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

›EXAMPLES · 9 of 19

NMR (CDCl 3 ) δ: 0.90 (9H, t, J=7.3 Hz), 1.19 (6H, m), 1.34 (6H, m), 1.53 (6H, m), 2.40 (3H, s), 2.61 (3H, s), 6.61 (1H, s).

Of the two main components, the fraction, which had been eluted later, was collected to give 6.04 g of 5-methyl-7-methylthio-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 0.92 (9H, t, J=7.3 Hz), 1.15 (6H, m), 1.35 (6H, m), 1.57 (6H, m), 2.39 (3H, s), 2.56 (3H, s), 6.92 (1H, s).

Preparation 23

7-N-Acetylaminomethyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

a) 7-N-Acetylaminomethylimidazo[5,1-b]thiazole

Hydrazine monohydrate (0.34 ml) was added to a solution of 0.63 g of 7-phthalimidomethylimidazo[5,1-b]thiazole in 15 ml of ethanol. The mixture was heated under reflux for one hr. The system was cooled to room temperature. The insolubles were removed by filtration. The solvent was removed by distillation. DMF (10 ml), 2 ml of pyridine and 1 ml of acetic anhydride were added the residue. The mixture was stirred at room temperature for 30 min. Methanol (5 ml) was added thereto. The solvent was removed by distillation. The residue was purified by column chromatography on silica gel (dichloromethane:methanol=20:1) to give 0.41 g of 7-N-acetylaminomethylimidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 2.02 (3H, s), 4.49 (2H, d, J=5.5 Hz), 6.25 (1H, s), 6.83 (2H, d, J=4.2 Hz), 7.37 (2H, d, J=4.2 Hz), 7.93 (1H, s).

b) 7-N-Acetylaminomethyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

A 1.6 N n-butyllithium/n-hexane solution (2.5 ml) was added to a solution of 0.24 g of 7-N-acetylaminomethylimidazo[5,1-b]thiazole in 10 ml of dry THF and 2 ml of HMPA in an argon atmosphere at −50° C. The mixture was stirred at the same temperature for 30 min. Tri-n-butylstannyl chloride (0.36 ml) was added thereto, followed by stirring for 30 min. A saturated aqueous ammonium chloride solution was added thereto. Ethyl acetate was then added, followed by washing with water and saturated brine in that order. The organic layer was dried over anhydrous magnesium sulfate. The solvent was removed by distillation. The residue was purified by column chromatography on silica gel, (dichloromethane:methanol=50:1) to give 0.42 g of the title compound.

NMR (CDCl 3 ) δ: 0.91 (9H, t, J=7.3 Hz), 1.14 (6H, t, J=8.4 Hz), 1.30-1.40 (6H, m), 1.50-160 (6H, m), 2.02 (3H, s), 4.48 (2H, d, J=5.3 Hz), 6.10 (1H, s), 7.12 (1H, s), 7.88 (1H, s).

Preparation 24

7-N,N-Dimethylcarbamoylacetyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

a) 7-[(2-N,N-dimethylcarbamoyl-1-hydroxy)ethyl]imidazo[5,1-b]thiazole

Dimethylacetamide (0.97 ml) was added to 10 ml of a 1.0 N lithiumbis(trimethylsilyl)amide/THF solution in an argon atmosphere at −70° C. The mixture was stirred at the same temperature for 30 min. A solution of 1.52 g of 7-formylimidazo[5,1-b]thiazole in, 40 ml of dry THF was added thereto. The mixture was stirred at the same temperature for 30 min. A saturated aqueous ammonium chloride solution was added thereto. Ethyl acetate was then added, followed by washing with water and saturated brine in that order. The organic layer was dried over anhydrous magnesium sulfate. The solvent was removed by distillation. The residue was purified by column chromatography on silica gel (dichloromethane:methanol=20:1) to give 1.04 g of 7-[(2-N,N-dimethylcarbamoyl-1-hydroxy)ethyl]imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 2.80 (1H, m), 2.97 (3H, s), 3.03 (3H, s), 3.03-3.10 (1H, m), 5.06 (1H, d, J=3.6 Hz), 5.27-5.35 (1H, m), 6.81 (1H, d, J=4.1 Hz), 7.35 (1H, d, J=4.1 Hz), 7.92 (1H, s).

b) 7-N,N-Dimethylcarbamoylacetylimidazo[5,1-b]thiazole

Manganese dioxide (2.84 g) was added to a solution of 1.04 g of 7-[(2-N,N-dimethylcarbamoyl-1-hydroxy)ethyl]imidazo[5,1-b]thiazole in 30 ml of dichloromethane. The mixture was stirred at room temperature for 12 hr. Manganese dioxide was removed by a filtration. The solvent was removed by distillation. The residue was purified by column chromatography on silica gel (dichloromethane:methanol=20:1) to give 0.98 g of 7-N,N-dimethylcarbamoylacetylimidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 3.01 (3H, s), 3.09 (3H, s), 4.18 (2H, s), 7.11 (1H, d, J=4.1 Hz), 7.56 (1H, d, J=4.1 Hz), 8.00 (1H, s).

c) 7-N,N-Dimethylcarbamoylacetyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

A 1.0 N lithiumbis(trimethylsilyl)amide/THF solution (2.1 ml) was added to a solution of, 0.24 g of 7-N,N-dimethylcarbamoylacetylimidazo[5,1-b]thiazole in 5 ml of dry THF in an argon atmosphere at −50° C. The mixture was stirred at the same temperature for 30 min. Tri-n-butylstannyl chloride (0.29 ml) was added thereto. The mixture was stirred for 30 min. A saturated aqueous ammonium chloride solution was added thereto. Ethyl acetate was then added, followed by washing with water and saturated brine in that order. The organic layer was dried over anhydrous magnesium sulfate. The solvent was removed by distillation. The residue was purified by column chromatography on silica gel (dichloromethane:methanol=20:1) to give 0.29 g of the title compound.

NMR (CDCl 3 ) δ: 0.91 (9H, t, J=17.1 Hz), 1.18 (3H, t, J=8.3 Hz), 1.30-1.40 (6H, m), 1.53-1.65 (6H, m), 3.00 (3H, s), 3.07 (3H, s), 4.18 (2H, s), 7.27 (1H, s), 7.94 (1H, s).

Preparation 25

7-N,N-Dimethylsulfamoyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

a) 7-Chlorosulfonylimidazo[5,1-b]thiazole

A solution of chlorosulfuric acid in 20 ml of carbon tetrachloride was added under ice cooling to a solution of 11.18 g of imidazo[5,1-b]thiazole in 200 ml of carbon tetrachloride. The reaction mixture was heated under reflux for 6 hr. Water was added thereto under ice cooling to terminate the reaction. The mixture was extracted with dichloromethane. The organic layers were combined together. The combined organic layers were washed with a dilute aqueous sodium hydroxide solution and saturated brine in that order and then dried over anhydrous magnesium sulfate. The solvent was removed by distillation. Isopropyl ether was added to the residue. The resultant powder was collected by filtration to give 4.01 g of 7-chlorosulfonylimidazo[5,1-b]thiazole.

›EXAMPLES · 10 of 19

NMR (CDCl 3 ) δ: 7.19 (1H, d, J=14.1 Hz), 7.65 (1H, d, J=4.1 Hz), 8.12 (1H, s).

b) 7-N,N-Dimethysulfamoylimidazo[5,1-b]thiazole

A 2 M THF solution (6 ml) of dimethylamine was added under ice cooling to a solution of 1.11 g of 7-chlorosulfonylimidazo[5,1-b]thiazole in 20 ml of THF. The mixture was stirred at room temperature for 30 min. Dichloromethane was added thereto, followed by washing with water and saturated brine in that order. The organic layer was dried over anhydrous magnesium sulfate. The solvent was removed by distillation. Ethyl acetate was added to the residue. The resultant powder was collected by filtration to give 1.10 g of 7-N,N-dimethylsulfamoylimidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 2.87 (6H, s), 7.03 (1H, d, J=4.2 Hz), 7.54 (1H, d, J=4.2 Hz), 8.05 (1H, s).

c) 7-N,N-Dimethylsulfamoyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

In substantially the same manner as in Preparation 4-b), 1.11 g of the title compound was obtained from 1.22 g of 7-N,N-dimethylsulfamoylimidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 0.92 (9H, t, J=7.2 Hz), 1.15-1.22 (6H, m), 1.30-1.40 (6H, m), 1.56-1.63 (6H, m), 2.86 (6H, s), 7.26 (1H, s), 7.97 (1H, s).

Preparation 26

Methyl 2-(tri-n-Butylstannyl)imidazo[5,1-b]thiazole 7-Carboxylate

a) Imidazo[5,1-b]thiazole-7-carboxylic Acid

A 0.95 M ethylmagnesium bromide/THF solution (12.6 ml) was added dropwise to a solution (50 ml) of 2.501 g of 7-iodoimidazo[5,1-b]thiazole in THF ac −70° C. The mixture was stirred for 30 min. Carbon dioxide (which had been evolved from about 5 g of dry ice and passed through a calcium chloride tube) was introduced into the reaction solution at the same temperature over a period of 40 min. The reaction solution was allowed to stand at −20° C. overnight, and then added to an ice cold mixed solution composed of an aqueous sodium hydroxide (0.41 g) solution (100 ml) and ether (200 ml) with stirring. The mixture was stirred for one hr. The organic layer was separated and concentrated under the reduced pressure by a minor amount, and the remaining organic solvent was removed by distillation. The residue was adjusted to pH 3.5 by the addition of 2 N hydrochloric acid under ice cooling. The resultant precipitate was washed with a minor amount of cold water, and then dried under the reduced pressure to give 1.407 g of imidazo[5,1-b]thiazole-7-carboxylic acid.

NMR (DMSO-d 6 ) δ: 7.44 (1H, d, J=4.1 Hz), 8.03 (1H, d, J=4.1 Hz), 8.29 (1H, s).

b) Methyl Imidazo[5,1-b]thiazole-7-carboxylate

Imidazo[5,1-b]thiazole-7-carboxylic acid (0.680 g) was suspended in 30 ml of water. Potassium carbonate (0.279 g) was added to the suspension. The mixture was stirred to prepare a homogeneous solution which was then lyophilized to give a potassium salt. DMF (25 ml) was added to the potassium salt. The mixture was ice cooled. Methyl iodide (0.633 g) was added thereto, followed by stirring for 18 hr under ice cooling. DMF was removed from the reaction solution by distillation under the reduced pressure.

Dichloromethane (100 ml) and 100 ml of a 15% aqueous sodium chloride solution were added to the residue for dissolution. The organic layer was separated. The aqueous layer was extracted with dichloromethane (50 ml, twice). The organic layers were combined together, dried over anhydrous magnesium sulfate, and then concentrated to a volume of 50 ml under the reduced pressure. Ethyl acetate (50 ml) was then added to the concentrate, followed by concentration to a volume of 20 ml. The concentrate was allowed to stand at 0° C. for 3 hr. The resultant crystal was collected by filtration, washed with a minor amount of cold ethyl acetate, and then dried under the reduced pressure to give 0.644 g of methyl imidazo[5,1-b]thiazole-7-carboxylate.

NMR (CDCl 3 ) δ: 3.96 (3H, s), 7.06 (1H, d, J=4.2 Hz), 7.55 (1H, d, J=4.2 Hz), 8.02 (1H, s).

c) Methyl 2-(tri-n-Butylstannyl)imidazo[5,1-b]thiazole-7-carboxylate

A solution (5 ml) of 0.716 g of tri-n-butylstannyl Chloride in THF was added to a solution (20 ml) of 0.364 g of methyl imidazo[5,1-b]thiazole-7-carboxylate in THF at −70° C. A 1.0 N lithiumbis(trimethylsilyl)amide/n-hexane solution (4.4 ml) was added dropwise thereto at −70° C. The mixture was stirred at −50° C. for 30 min. The reaction solution was added to an ice cold mixed solution composed of 50 ml of 0.2 N phosphate buffer (ph 7) and 50 ml of dichloromethane with stirring. The organic layer was separated, and then dried over anhydrous magnesium sulfate. The solvent was removed by distillation. The residue was subjected to separation and purification by flash column chromatography on silica gel (hexane:ethyl acetate=1:1) to give 0.395 g of the title, compound.

NMR (CDCl 3 ) δ: 0.92 (9H, t, J=7.3 Hz), 1.42-1.06 (12H, m), 1.64-1.52 (6H, m), 3.94 (3H, s), 7.26 (1H, s), 7.95 (1H, s).

Preparation 27

7-(N-Methoxy-N-methylsulfamoyl)-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

a) 7-(N-Methoxy-N-methylsulfamoyl)imidazo[5,1-b]thiazole

N,O-Dimethylhydroxylamine hydrochloride (0.23 g) and 0.56 ml of triethylamine were added to a solution of 0.44 g of 7-chlorosulfonylimidazo[5,1-b]thiazole in 5 ml of DMF. The mixture was stirred at room temperature for one hr. Ethyl acetate was added thereto, followed by washing with water and saturated brine in that order. The organic layer was dried over anhydrous magnesium sulfate. The solvent was removed by distillation. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=1:2) to give 0.44 g off 7-(N-methoxy-N-methylsulfamoyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 3.05 (H, s), 3.83 (3H, s), 7.07 (1H, d, J=4.2 Hz), 7.58 (1H, d, J=4.21 Hz), 8.09 (1H, s).

b) 7-(N-Methoxy-N-methylsulfamoyl)-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

A 1.0 N lithiumbis(trimethlylsilyl)amide/THF solution (2.0 ml) was added to a solution of 0.44 g of 7-(N-methoxy-N-methylsulfamoyl)imidazo[5,1-b]thiazole in 9 ml of dry THF in an argon atmosphere at −4° C. The mixture was stirred at the same temperature for 30 min. Tri-n-butylstannyl chloride (0.58 ml) was added thereto. The mixture was stirred for 30 min. Further, a 1.0 N lithiumbis(trimethylsilyl)amide/THF solution (2.5 ml) was then added, followed by stirring for 30 min. Tri-n-butylstannyl chloride (0.1 ml) was added thereto. The mixture was stirred at the same temperature for 30 min. A saturated aqueous ammonium chloride solution was added thereto, and the ethyl acetate was then added, followed by washing with water and saturated brine in that order. The organic layer was dried over anhydrous magnesium sulfate. The solvent was removed by distillation. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=1:2) to give 0.39 g of the title compound.

›EXAMPLES · 11 of 19

NMR (CDCl 3 ) δ: 0.92 (9H, t, J=71.2 Hz), 1.16-1.25 (6H, m), 1.35-1.45 (6H, m), 1,55-1.65 (6H, m), 3.05 (3H, s), 3.84 (3H, s), 7.26 (1H, s), 8.00 (1H, s).

Preparation 28

7-Trifluoroacetyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

a) 7-Trifluoroacetylimidazo[5,1-b]thiazole

A 1 M ethylmagnesium bromide/THF solution (10 ml) was added to a solution of 2.50 g of 7-iodoimidazo[5,1-b]thiazole in 10 ml of dry THF in an argon atmosphere at −50° C. The mixture was stirred at the same temperature for one hr. Trifluoroacetic anhydride (1.53 ml), was added thereto, followed by stirring at the same temperature for 10 min. A saturated aqueous ammonium chloride solution was added to the reaction mixture. Ethyl acetate was then added, followed by washing with a dilute aqueous sodium thiosulfate solution and saturated brine in that order. The organic layer was dried over anhydrous magnesium sulfate. The solvent was removed by distillation. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=1:1) to give 0.64 g of 7-trifluoroacetylimidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 7.25 (1H, d, J=14.1 Hz), 7.68 (1H, d, J=4.1 Hz), 8.13 (1H, s).

b) 7-Trifluoroacetyl-2-tri-n-butylstannyl)imidazo[5,1-b]thiazole

A 1.0 N lithiumbis(trimethylsilyl)amide/THF solution (2.0 ml.) was added to a solution of 0.34 g of 7-trifluoroacetylimidazo[5,1-b]thiazole and 0.48 ml of tri-n-butylstannyl chloride in 16 ml of dry THF in an argon atmosphere at −40° C. The mixture was stirred at the same temperature for 30 min. A saturated aqueous ammonium chloride solution was added thereto. Ethyl acetate was then added, followed by washing with water and saturated brine in that order. The organic layer was dried over anhydrous magnesium sulfate. The solvent was removed by distillation. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=4:1) to give 0.14 g of the title compound.

NMR (CDCl 3 ) δ: 0.92 (9H, t, J=7.4 Hz), 1.20-1.40 (12H, m), 1.55-1.70 (6H, m), 7.38 (1H, s), 8.05 (1H, s).

Preparation 29

7-(t-Butyldimethylsilylsulfamoyl)-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

a) 7-Sulfamoylimidazo[5,1-b]thiazole

A 2 M ammonia/methanol solution, (4 ml) was added to a solution of 0.44 g of 7-chlorosulfonylimidazo[5,1-b]thiazole in 10 ml of THF. The mixture was stirred at room temperature for 12 hr. The reaction mixture was concentrated. The residue was purified by column chromatography on silica gel (dichloromethane:methanol=10:1) to give 0.34 g of 7-sulfamoylimidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 7.33 (2H, s), 7.38 (1H, d, J=4.1 Hz), 8.00 (1H, d, J=4.1 Hz), 7.32 (1H, s).

b) 7-(t-Butyldimethylsilylsulfamoyl)imidazo[5,1-b]thiazole

t-Butyldimethylsilyl chloride (0.30 g) and 0.33 ml of triethylamine were added to a solution of 0.20 g of 7-sulfamoylimidazo[5,1-b]thiazole in 5 ml of DMF. The mixture was stirred at room temperature for one hr. Ethyl acetate was added to the reaction mixture, followed by washing with water and saturated brine in that order. The organic layer was dried over anhydrous magnesium sulfate. The solvent was removed by distillation. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=1:1) to give 0.34 of 7-(t-butyldimethylsilylsulfamoyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 0.24 (6H, s), 0.82 (9H, s), 4.54 (1H, s), 7.00 (1H, d, J=4.2 Hz), 7.50 (1H, d, J=4.2 Hz), 8.02 (1H, s).

c) 7-(t-Butyldimethylsilylsulfamoyl)-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

In substantially the same manner as in Preparation 28-b), 0.73 g of the title compound was obtained from 0.52 g of 7-(t-butyldimethylsilylsulfamoyl)imidazo[5,1-b]thiazole and 0.53 ml of tri-n-butylstannyl chloride.

NMR (CDCl 3 ) δ: 0.24 (6H, s), 0.88-0.96 (21H, m), 1.18 (6H, t, J=8.4 Hz), 1.30-1.40 (6H, s), 1.55-1.65 (6H, m), 4.52 (1H, s), 7.21 (1H, s), 7.94 (1H, s).

Preparation 30

7-(2-Methoxycarbonylvinyl)-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole (a Mixture of Geometrical Isomers)

a) 7-(2-Methoxycarbonylvinyl)imidazo[5,1-b]thiazole (a Mixture of Geometrical Isomers)

Methyl triphenylphosphoranylideneacetate (500 mg) was added to a solution of 150 mg of 7-formylimidazo[5,1-b]thiazole in 15 ml of methanol. The mixture was stirred at room temperature for 15 min. Ethyl acetate was added thereto. The mixture was washed with water, dried over anhydrous magnesium sulfate, and filtered. The solvent was removed by distillation under the reduced pressure. The residue was purified by column chromatography on silica gel(chloroform:methanol=20:1) to give 228 mg of 7-(2-methoxycarbonylvinyl)imidazo[5,1-b]thiazole (a mixture of geometrical isomers).

NMR (CDCl 3 ) δ: 3.80 (3H, s), 6.17 (1H, d, J=15.8 Hz), 7.01 (1H, d, J=4.1 Hz), 7.50 (1H, d, J=4.1 Hz), 7.77 (1H, d, J=15.8 Hz), 8.05 (1H, s); NMR (CDCl 3 ) δ: 3.81 (3H, s), 5.82 (1H, d, J=12.4 Hz), 7.03 (1H, d, J=4.1 Hz), 7.13 (1H, d, J=12.4 Hz), 7.50 (1H, d, J=4.1 Hz), 8.06 (1H, s).

b) 7-(2-Methoxycarbonylvinyl)-2-(tri-n-butylstannyl(imidazo[5,1-b]thiazole (a Mixture of Geometrical Isomers)

Tri-n-butylstannyl chloride (250 μl) and 2.1 ml of a 1.0 N lithiumbis(trimethylsilyl)amide/THF solution were added in that order to a solution of 7-(2-methoxycarbonylvinyl)imidazo[5,1-b]thiazole (a mixture of geometrical isomers) in dry THF in an argon atmosphere at −78° C. The mixture was stirred at the same temperature for 15 min. Water was added thereto. The mixture was extracted with ethyl acetate, followed by washing with saturated brine. The extract was dried over anhydrous magnesium sulfate and then filtered. The solvent was removed by distillation under the reduced pressure. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=4:1) to give 408 mg of the title compound.

NMR (CDCl 3 ) δ: 0.92 (9H, t, J=7.4 Hz), 1.18 (6H, m), 1.36 (6H, m), 1.58 (6H, m) 3.78 (3H, s), 6.13 (1H, d, J=15.8 Hz), 7.23 (1H, s), 7.77 (1H, d, J=15.8 Hz), 7.98 (1H, s);

NMR (CDCl 3 ) δ: 0.92 (9H, t, J=7.4 Hz),1.18 (6H, m), 1.36 (6H, m), 1.58 (6H, m), 3.82 (3H, s), 5.77 (1H, d, J=12.4 Hz), 7.10 (1H, d, J=12.4 Hz), 7.25 (1H, s), 8.01 (1H, s).

›EXAMPLES · 12 of 19

Preparation 31

7-(Thiazol-4-yl)-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

a) 7-Chloroacetylimidazo[5,1-b]thiazole

Chloroacetyl chloride (5.97 ml) was added to a solution of 12.5 g of aluminum chloride in 40 ml of 1,2-dichloroethane. The mixture was stirred at room temperature for 20 min. A solution of 1.93 g of imidazo[5,1-b]thiazole in 20 ml of 1,2-dichloroethane was added thereto. The mixture was heated under reflux for 2 hr. Water was added thereto, followed by extraction with dichloromethane. The organic layers were combined together. The combined organic layers were washed with a dilute aqueous sodium hydroxide solution and saturated brine in that order. The solvent was removed by distillation. Isopropyl ether was added to the residue. The resultant powder was collected by filtration to obtain the title compound.

NMR (CDCl 3 ) δ: 4.83 (2H, s), 7.16 (1H, d, J=4.1 Hz), 7.60 (1H, d, J=4.1 Hz), 8.02 (1H, s)

b) 7-(Thiazol-4-yl)imidazo[5,1 b]thiazole

Diphosphorus pentasulfide (846 mg) was added to 8.4 ml of formamide. The mixture was stirred at room temperature overnight. 7-Chloroacetylimidazo[5,1-b]thiazole (2.32 g) was added to the reaction solution. The mixture was stirred at room temperature for 15 hr. Water (20 ml) and 10 ml of dichloromethane were added thereto The mixture was adjusted to pH 8.8 by gradually adding a sodium hydrogencarbonate powder. Extraction was carried out six times with 50 ml of dichloromethane. The organic layer was dried over anhydrous magnesium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by column chromatography on silica gel (hexane ethyl acetate=1 2) to give 1.72 g of 7-(thiazol-4-yl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 6.93 (1H, d, J=4.2 Hz), 7.46 (1H, d, J=4.2 Hz), 7.60 (1H, d, J=2.1 Hz), 8.05 (1H, s)8.87 (1H, d, J=2.1 Hz); MS (EI): 207 (M + )

c) 7-(Thiazol-4-yl)-2-(tri-n-butylstannyl) imidazo[5,1-b]thiazole

A solution of 1.01 g of 7-(thiazol-4-yl)imidazo[5,1-b]thiazole in 45 ml of THF was cooled to −70° C. in an argon atmosphere. Tri-n-butylstannyl chloride (1.58 ml) was added thereto. A 1 N lithiumbis(trimethylsilyl)amide/THF solution (11.2 ml) was added dropwise at the same temperature. The mixture was stirred for 30 min. The temperature of the mixture was raised to −30° C. over a period of one hr. A saturated aqueous sodium chloride solution was added thereto, followed by extraction twice with ethyl acetate. The extract was dried over anhydrous magnesium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=1:1). The title compound (294 mg) was obtained from the fraction of Rf=0.5.

NMR (CDCl 3 ) δ: 0.92 (9H, t J=Hz), 1.20 (6H, m), 1.37 (6H, m), 1.58 (6H, m), 7.22 (1H, s), 7.59 (1H, d, J=2.2 Hz), 8.00 (1H, s) 8.87 (1H, d, J=2.2 Hz).

Preparation 32

7-t-Butyldimethylsilyloxyacetyl-5-methyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

a) 7-Acetoxyacetyl-5-methylimidazo[5,1-b]thiazole

In the same manner as in Preparation 16-a), 734 mg of 7-acetoxyacetyl-5-methylimidazo[5,1-b]thiazole was obtained from 821 mg of 7-acetyl-5-methylimidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 2.23 (3H, s), 2.,63 (3H, s), 5.40 (2H, s), 7.08 (1H, d, J=4.1 Hz), 7.39 (1H, d, J=4.1 Hz).

b) 7-Hydroxyacetyl-5-methylimidazo[5,1-b]thiazole

In the same manner as in Preparation 16-b), 704 mg of 7-hydroxyacetyl-5-methylimidazo[5,1-b]thiazole was obtained from 872 mg of 7-acetoxyacetyl-5-methylimidazo[5,1-b]thiazole.

NMR (DMSO-d 6 ) δ: 2.56 (3H, s), 4.63 (2H, s), 7.49 (1H, d, J=3.7 Hz), 8.05 (1H, d, J=3.71Hz).

c) 7-t-Butyldimethylsilyloxyacetylimidazo[5,1-b]thiazole

In the same manner as in Preparation 16-c), 699 mg of 7-t-butyldimethylsilyloxyacetyl-5-methylimidazo[5,1-b]thiazole was obtained from 508 mg of 7-hydroxyacetyl-5-methylimidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 0.15 (6H, s), 0.196 (9H, s), 2.63 (3H, s), 5.04 (2H, s), 7.05 (1H, d, J=4.1 Hz), 7.36 (1H, d, J=4.1 Hz).

d) 7-t-Butyldimethylsilyloxyacetyl-5-methyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

7t-Butyldimethylsilyloxyacetyl-5-methylimidazo-[5,1-b]thiazole (49.5 mg) was dissolved in 2 ml of THF and 0.4 ml of HMPA. Tri-n-butylstannyl chloride (0.059 ml) and 0.319 ml of a 1.0 N lithiumbis(trimethylsilyl)amide/THF solution were added dropwise in that order to the solution in an argon atmosphere at −73° C. The mixture was stirred at the same temperature for one hr. A 1.0 N lithiumbis(trimethylsilyl)amide/THF solution (0.160 ml) was added dropwise thereto. The mixture was stirred at the same temperature for additional 40 min. An ammonium chloride solution was added to the reaction solution, followed by extraction with ethyl acetate and washing three times with brine. The extract was dried over anhydrous magnesium sulfate and then filtered. The solvent was removed by distillation under the reduced pressure. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=5:1) to give 66.9 mg of the title compound.

NMR (CDCl 3 ) δ: 0.15 (6H, m), 0.91 (9H, t, J=7.4 Hz), 0.96 (9H, s), 1.18 (6H, m), 1.35 (6H, m), 1.58 (6H, m), 2.62 (3H, s), 5.03 (2H, s), 7.06 (1H, s).

Preparation 33

7-Methanesulfonylaminoacetyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

a) 7-Methanesulfonylaminoacetylimidazo[5,1-b]thiazole

2 N hydrochloric acid (4.88 ml) land 336 mg of 10%Pd—C were added to a solution of 673 mg of 7-azidoacetylimidazo[5,1-b]thiazole in 16 ml of water and 20 ml of THF. The atmosphere in the reactor was replaced with hydrogen. The system was stirred at room temperature for 2 hr. The catalyst was removed by filtration through Celite and then washed with water. THF was removed by distillation under the reduced pressure. A 1 N aqueous sodium hydroxide solution (12.8 ml) was added thereto, followed by extraction nine times with dichloromethane. The organic layers were combined together, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under the reduced pressure. The residue was dissolved in 20 ml of dichloromethane. N,N-diisopropylethylamine (0.849 ml) and 0.377 ml of methanesulfonyl chloride were added to the solution. The mixture was stirred at room temperature for one hr. An aqueous sodium hydrogencarbonate solution was added to the reaction solution, followed by extraction three times with dichloromethane. The organic layers were combined together, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under the reduced pressure. The residue was purified by column chromatography on silica gel (dichloromethane:methanol=30:1) to give 397 mg of 7-methanesulfonylaminoacetylimidazo[5,1-b]thiazole.

›EXAMPLES · 13 of 19

NMR (DMSO-d 6 ) δ: 2.98 (3H, s), 4.51 (2H, d, J=5.7 Hz), 7.36 (1H, t, J=5.7 Hz), 7.55 (1H, d, J=4.2 Hz), 8.12 (1H, d, J=4.2 Hz), 8.37 (1H, s).

b) 7-Methanesulfonylaminoacetyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

7-Methanesulfonylaminoacetylimidazo[5,1-b]thiazole (46.2 mg) was dissolved in 2 ml of THF and 0.4 ml of HMPA. Tri-n-butylstannyl chloride (0.076 ml) and 0.713 ml of a 1.0 N lithiumbis(trimethylsilyl)amide/THF solution were added dropwise in that order to the solution in an argon atmosphere at −70° C. The mixture was stirred at the same temperature for 1.5 hr. A 1.59 N n-butyllithium/n-hexane solution (0.146 ml) was added dropwise thereto. The mixture was stirred at the same temperature for one hr. A 1.59 N n-butyllithium/n-hexane solution ((0.146 ml) and 0.076 ml of tri-n-butylstannyl chloride were added dropwise thereto. The mixture was stirred at the same temperature for 45 min. An ammonium chloride solution was added to the reaction solutions, followed by extraction with ethyl acetate. The organic layer was washed twice with brine, dried over anhydrous magnesium sulfate, and filtered. The solvent was removed by distillation under the reduced pressure. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=1:1) to give 37.5 mg of the title compound.

NMR (CDCl 3 ) δ: 0.92 (9H, t, J=7.4 Hz), 1.20 (6H, m), 1.35 (6H, m), 1.60 (6H, m), 3.00 (3H, s), 4.69 (2H, d, J=5.0 Hz), 5.44 (1H, br), 7.32 (1H, s), 7.96 (1H, s).

Preparation 34

7-Methanesulfonylaminomethyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

a) 7-(Methanesulfonylaminomethyl)imidazo[5,1-b]thiazole

Triethylamine (0.18 ml) and 0.075 ml of methanesulfonyl chloride were added in that order under ice cooling to a solution of 134 mg of 7-aminomethylimidazo[5,1-b]thiazole in 2.5 ml of dry dichloromethane. In this state, the system was stirred for 2 hr while gradually raising the temperature to room temperature. The reaction solution was diluted with 20 ml of dichloromethane, followed by washing with saturated brine. The aqueous layer was extracted with 10 ml of dichloromethane. The organic layers were combined together, dried over anhydrous magnesium sulfate, and filtered. The solvent was removed by distillation. The oil thus obtained was purified using Sephadex LH-20 (dichloromethane:methanol=1:1) to give 30 mg of 7-(methanesulfonylaminomethyl)imidazo[5,1-b]thiazole as a light yellow solid.

NMR (CDCl 3 ) δ: 2.91 (3H, s), 4.43 (2H, d, J=6.0 Hz), 5.26 (1H, br.t), 6.87 (1H, d, J=4.2 Hz), 7.40 (1H, d, J=4.2 Hz), 7.99 (1H, s); MS (TSP): m/z=232 (M + +H)

b) 7-Methanesulfonylaminomethyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

A solution of 231 mg of 7-(methanesulfonylaminomethyl)imidazo[5,1-b]thiazole dissolved in a mixed solution composed of 10 ml of dry THF and 1 ml of dry HMPA was cooled to −5° C. with stirring. A 1.6 N n-butyllithium/n-hexane solution (2.0 ml) was added dropwise to the mixed solution in an argon atmosphere at −51 to −49° C. over a period of 15 min . The mixture was stirred at the same temperature for 15 min. Further, 0.34 ml of tri-n-butylstannyl chloride was added dropwise thereto at −50 to −48° C. over a period of 10 min. The mixture was stirred at −50 to −40° C. for 140 min. Tri-n-butylstannyl chloride (0.07 ml) was additionally added to the reaction solution at −42° C. The mixture was stirred for 30 min. 0.38 M phosphate buffer (pH 6.0) (15 ml) was added thereto. The mixed solution was extracted with 30 ml of ethyl acetate. The organic layer was washed with 0.38 M phosphate buffer (pH 6.0) and saturated brine in that order, and then dried over anhydrous sodium sulfate. The anhydrous magnesium sulfate was removed by filtration. The solvent was removed by distillation. The brown oil thus obtained was purified by column chromatography on silica gel (eluting with dichloromethane:ethyl acetate=1:1 and then with ethyl acetate only) to give 160 mg of the title compound as a yellow crystal.

NMR (CDCl 3 ) δ: 0.92 (9H, t, J=72 Hz), 1.05-1.20 (6H, 1 m), 1.25-1.40 (6H, m), 1.45-1.70 (6H, m), 2.91 (3H, s), 4.41 (2H, d, J=5.8 Hz), 5.03 (1H, br.t), 7.14 (1H, s), 7.92 (1H, s); MS (FAB + ): m/z=522 (M + +H), 520 (M + −2+H).

Preparation 35

7-(N,N-Dimethylaminosulfonylamino)acetyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

a) 7-(N,N-Dimethylaminosulfonylamino)acetyl-imidazo[5,1-b]thiazole

7-Azidoacetylimidazo[5,1-b]thiazole (207 mg) was dissolved in 6 ml of THF, 4.5 ml of water, and 3 ml of 1 N aqueous hydrochloric acid. 10%Pd—C (103 mg) was added to the solution. The air in the reactor was replaced by hydrogen. The system was then stirred at room temperature for 17 hr. The catalyst was removed by filtration through Celite, followed by washing with water. The filtrate was concentrated to half the amount thereof. A 1 N aqueous sodium hydroxide solution (4 ml) was added to the filtrate. The mixture was extracted six times with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was dissolved in 5 ml of dichloromethane. N,N-diisopropylethylamine (0.783 ml) and 0.322 ml of N,N-dimethylaminosulfonyl chloride were added to the solution. The mixture was stirred at room temperature for 7 hr. An aqueous sodium hydrogencarbonate solution was added to the reaction solution. The mixture was extracted with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by column chromatography on silica gel (dichloromethane:methanol=30:1) to give 167 mg of 7-(N,N-dimethylaminosulfonylamino)acetyl-imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 2.83 (6H, s), 4.59 (2H, d, J=4.9 Hz), 5.45 (1H, br·s), 7.17 (1H, d, J=4.1 Hz), 7.62 (1H, d, J=4.1 Hz), 8.03 (1H, s).

b) 7-(N,N-Dimethylaminosulfonylamino)acetyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

Tri-n-butylstannyl chloride (0.962 ml) and 8.42 ml of a 1.0 N lithiumbis(trimethylsilyl)amide/THF solution were sequentially added at −73° C. in an argon atmosphere to a solution of 485 mg of 7-(N,N-dimethylaminosulfonylamino)acetyl-imidazo[5,1-b]thiazole in 18 ml of THF. The mixture was stirred at the same temperature for 30 min. An aqueous ammonium chloride solution was added to the reaction solution. The mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate, and then filtered. The solvent was removed by distillation under the reduced pressure. The residue !was purified by column chromatography on silica gel (hexane:ethyl acetate=1:1) to give 427 mg of the title compound.

›EXAMPLES · 14 of 19

NMR (CDCl 3 ): 0.92 (9H, t, J=7.3 Hz), 1.15-1.25 (6H, m), 1.3-1.45 (6H, m), 1.5-1.7 (6H, m), 2.83 (6H, s), 4.58 (2H, d, J=4.7 Hz), 5.47 (1H, br·s), 7.31 (1H, s), 7.95 (1H, s).

Preparation 36

7-[2-(4-Nitrobenzyloxycabonyl)aminoethanesulfonylamino]acetyl-2-(tri-n-butylstannyl)-imidazo[5,1-b]thiazole

a) 7-[2-(4-Nitrobenzyloxycarbonyl)aminoethanesulfonylamino]acetylimidazo[-5,1-b]-thizole

7-Azidoacetylimidazo[5,1-b]thiazole (685 mg) was dissolved in 20 ml of THF, 15 ml of water and 10 ml of 1 N aqueous hydrochloric acid. 10%Pd—C. (341 mg) was added to the solution. The air in the reactor was replaced by hydrogen. The system was stirred at room temperature for 2 hr. The catalyst was removed by filtration through Celite, followed by washing with water. The filtrate was concentrated to half of the amount thereof . A 1 N aqueous sodium hydroxide solution (13 ml) was added to the concentrate. The mixture was extracted six time with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was dissolved in 10 ml of dichloromethane. N,N-Diisopropylethylamine (0.865 ml) and 1.60 g of 2-(4-nitrobenzyloxycarbonyl)aminoethanesulfonyl chloride were added to the solution under ice cooling. The mixture was stirred at the same temperature for one hr. An aqueous sodium hydrogencarbonate solution was added to the reaction solution. The mixture was extracted with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by column chromotography on silica gel (dichloromethane:methanol 30:1) to give 8108 mg of 7-[2 -(4-nitrobenzyloxycarbonyl)aminoethanesulfonylamino]acetylimidazo[5,1-]thiazole.

NMR (CDCl 3 ): 3.25-3.35 (2H, m), 3.7-3.8 (2H, m), 4.69 (2H, d, J=5.0 Hz), 5.20 (2H, s), 5.49 (1H, br·s), 5.75 (1H, br·s), 7.17 (1H, d, J=4.2 Hz), 7.50 (2H, d, J=8.7 Hz), 7.60 (1H, d, J=4.2 Hz), 8.02 (1H, s), 8.19 (2H, d, J=8.7 Hz).

b) 7-[2-(4-Nitrobenzyloxycarbonyl)aminoethanesulfonylamino]acetyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

Tri-n-butylstannyl chloride (0.83 ml) and 7.3 ml of a 1.0 N lithiumbis(trimethylsilyl)amide/THF solution were sequentially added at −73° C. in an argon atmosphere to a solution of 682 mg of 7-[2-(4-Nitrobenzyloxycarbonyl)aminoethane-sulfonylamino]acetylimidazo[5,1-b]thiazole in 16 ml of THF and 3 ml of HMPA. The mixture was stirred at the same temperature for 30 min. An aqueous ammonium chloride solution was added to the reaction solution. The mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and then filtered. The solvent was removed by distillation under the reduced pressure. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=1:1-1:2) to give 327 mg of the title compound.

NMR (CDCl 3 ) δ: 0.91 (9H, t, J=7.3 Hz), 1.15-1.25 (6H, m), 1.25-1.4 (6H, m), 1.5-1.65 (6H, m), 3.25-3.35 (2H, m), 3.7-3.8 (2H, m), 4.68 (2H, d, J=5.1 Hz), 5.19 (2H, s), 5.60 (1H, br·s), 5.85 (1H, br·s), 7.32 (1H, s), 7.49 (2H, d, J=8.8 Hz), 7.96 (1H, s), 8.18 (2H, d, J=8.8 Hz).

Preparation 37

7-Phenylthio-2-(tri-n-butylstannyl)imidazo-[5,1-b]thiazole

a) 7-Phenylthioimidazo[5,1-b]thiazole

A 1 M ethylmagnesium bromide/THF solution (3.46 ml) was added in an argon atmosphere under ice cooling to a solution of 840 mg of 7-iodoimidazo[5,1-b]thiazole in 20 ml of dry THF. The mixture was stirred at the same temperature for one hr. Phenylbenzenethiol sulfonate (939 mg) was added thereto, and the mixture was stirred at the same temperature for one hr. A saturated aqueous ammonium chloride solution was added to the reaction mixture. Ethyl acetate was added thereto. The mixture was washed with a dilute aqueous sodium thiosulfate solution and saturated brine in that order. The organic layer was dried over anhydrous magnesium sulfate. The solvent was removed by distillation. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=1:1) to give 385 mg of 7-phenylthioimidazo[5,1-b]thiazole.

NMR (CDCl 3 ): 6.90 (1H, d, J=4.3 Hz), 7.1-7.2 (1H, m), 7.2-7.25 (5H, m), 7.45 (1H, d, J=4.3 Hz), 8.09 (1H, s).

b) 7-Phenylthio-2-4tri-n-butylstannyl)imidazo[5,1-b]thiazole

A 1.59 N n-butyl lithium/n-hexane solution (0.189 ml) was added dropwise at −73° C. in an argon atmosphere to a solution of 66.5 mg of 7-phenylthioimidazo[5,1-b]thiazole in 3 ml of THF. Subsequently, 0.098 ml of tri-n-butylstannyl chloride was added to the mixture. The mixture was stirred at the same temperature for 15 min. The temperature of the system was raised to −40° C. A 1.0 N lithiumbis(trimethylsilyl)amide/THF solution (0.11 ml) was added thereto. The mixture was stirred for one hr. An aqueous ammonium chloride solution was added to the reaction solution. The mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate, and then filtered. The solvent was removed by distillation under the reduced pressure. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=5:1) to give 115 mg of the title compound.

NMR (CDCl 3 ): 0.91 (9H, t, J=7.2 Hz), 1.1-1.2 (6H, m), 1.3-1.4 (6H, m), 1.5-1.7 (6H, m), 7.05-7.15 (1H, m), 7.15-7.25 (6H, m), 8.03 (1H, s)

Preparation 38

7-Ethylthio-2-(tri-n-butylstannyl)imidazo-[5,1-b]thiazole

a) Ethylethanethiol Sulfonate

Diethyl disulfide (3.69 ml) was dissolved in 450 ml of dichloromethane. 3-Chloroperbenzoic acid (19.43 g) was added under ice cooling to the solution. The mixture was stirred at room temperature for 3 hr. The insolubles were removed by filtration. The filtrate was washed with an aqueous sodium thiosulfate solution, an aqueous sodium hydrogencarbonate solution, and brine in that order, dried over anhydrous magnesium sulfate, and then filtered. The solvent was removed by distillation under the reduced pressure. The residue was purified by column chromatography on silica gel(hexane:ethyl acetate=5:1) to give 2.05 g of ethylethanethiol sulfonate.

›EXAMPLES · 15 of 19

NMR (CDCl 3 ): 1.44 (3H, t, J=7.4 Hz), 1.48 (3H, t, J=7.4 Hz), 3.16 (2H, q, J=7.4 Hz) 3.33 (2H, q, J=7.4 Hz).

7-Ethylthioimidazo[5,1-b]thiazole

A 1 M ethylmagnesium bromide/THF solution (8.52 ml) was added in an argon atmosphere under ice cooling to a solution of 2.07 g of 7-iodoimidazo[5,1-b]thiazole in 40 ml of dry THF. The mixture was stirred at the same temperature for one hr. Ethylethanethiol sulfonate (1.527 g) was added thereto, and the mixture was stirred at room temperature for 30 min. A saturated aqueous ammonium chloride solution was added to the reaction mixture. Ethyl acetate was a then added thereto, followed by washing with a dilute aqueous sodium thiosulfate solution and saturated brine in that order. The organic layer was dried over anhydrous magnesium sulfate. The solvent was removed by distillation. The residue was purified by column, chromatography on silica gel (dichloromethane:ethyl acetate=1:1) to give 1.064 g of 7-ethylthioimidazo[5,1-b]thiazole.

NMR (CDCl 3 ): 1.26 (3H, t, J=7.4 Hz), 2.83 (2H, q, J=7.4 Hz), 6.87 (1H, d, J=4.2 Hz), 7.40 (1H, d, J=4.2 Hz), 8.01 (1H, s).

c) 7-Ethylthio-2-(tri-n-but imidazo[5,1-b]thiazole

In the same manner as in Preparation 37-b), 2.34 g of the title compound was obtained from 1.10 g of 7-ethylthioimidazo[5,1-b]thiazole.

NMR (CDCl 3 ): 0.92 (9H, t, J=7.4 Hz), 1.1-1.2 (6H, m), 1.27 (3H, t, J=7.3 Hz), 1.3-1.4 (6H, m), 1.5-1.65 (6H, m), 2.82 (2H, q, J=7.3 Hz), 7.14 (1H, s), 7.95 (1H, s).

Preparation 39

3-Methyl-7-methylthio-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

a) 7-Iodo-3-methylimidazo[5,1-b]thiazole

In the same manner as in Preparation 22-a), 525 mg of 7-iodo-3-methylimidazo[5,1-b]thiazole was obtained from 505 mg of 3-methylimidazo[5,1-b]thiazole.

NMR (CDCl 3 ): 2.40 (3H, s), 6.46 (1H, s), 7.84 (1H, s).

b) 3-Methyl-7-methylthioimidazo[5,1-b]-thiazole

In the same manner as in Preparation 12-a), 1.88 g of 3-methyl-7-methylthioimidazo-[5,1-b]thiazole was obtained from 3.0 g of 7-iodazo-3-methylimidazo[5,1-b]thiazole.

NMR (CDCl 3 ): 2.40 (3H, s), 2.43 (3H, s), 6.44 (1H, s), 7.89 (1H, s).

c) 3-Methyl-7-methylthio-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

In the same manner as in Preparation 4-b), 4.70 g of the title compound was obtained from 2.15 g of 3-methyl-7-methylthioimidazo[5,1-b]thiazole.

NMR (CDCl 3 ): 0.91 (9H, t, J=7.3 Hz), 1.1-1.2 (6H, m), 1.25-1.4 (6H, m)., 1.5-1.65 (6H, m), 2.36 (3H, s), 2.42 (3H, s), 7.81 (1H, s).

Preparation 40

3-t-Butyldimethylsilyloxymethyl-7-methyl-thio-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

a) 3-t-Butyldimethylsilyloxymethyl-7-iodoimidazo-[5,1-b]thiazole

In the same manner as in Preparation 22-a), 3.21 g of 3-t-butyldimethylsilyloxymethyl-7-iodoimidazo-[5,1-b]thiazole was obtained from 26 g of 3-t-butyldimethylsilyloxymethylimidazo[5,1-b]-thiazole.

NMR (CDCl 3 ): 0.10 (6H, s), 0.90 (9H, s), 4.75 (2H, s), 6.66 (1H, s), 7.98 (1H, s).

b) 3-t-Butyldimethylsilyloxymethyl-7-methyl-thioimidazo[5,1-b]thiazole

In the same manner as in Preparation 12-a), 1.06 g of 3-t-butyldimethylsilyloxymethyl-7-methylthioimidazo[5,1-b]thiazole was obtained from 1.70 g of 3-t-butyldimethylsilyloxymethyl-7-iodoimidazo[5,1-b]thiazole.

NMR (CDCl 3 ): 0.11 (6H, s), 0.91 (9H, s), 2.44 (3H, s), 4.76 (2H,!s), 6.64 (1H, s), 8.02. (1H, s).

c) 3-t-Butyldimethylsilyloxymethyl-7-methylthio-2-(tri-n-butylstannyl)imidazo[5,1-b]-thiazole

In the same manner as in Preparation 4-b), 1.77 g of the title compound was obtained from 1.06 g of 3-t-butyldimethylsilyloxymethyl-7-methylthioimidazo[5,1-b]thiazole.

NMR (CDCl 3 ): 0.14 (6H, s), 0.91 (9H, t, J=7.4 Hz), 0.92 (9H, s), 1.1-1.2 (6H, m), 1.3-1.4 (6H, m), 1.5-1.65 (6H, m), 2.43 (3H, s), 4.66 (2H, s), 7.99 (1H, s).

Preparation 41

3-Azidomethyl-2-(tri-t-butylstannyl)imidazo[5,1-b]thiazole

a) 3-Azidomethylimidazo[5,1-b]thiazole

Diphenylphosphoryl azide (0.259 ml) and 0.157 ml of 1,8-diazabicyclo[5,4,0]-7-undecene were added to suspension of 154 mg of 3-hydroxymethylimidazo[5,1-b]thiazole in 2 ml of toluene. The mixture was stirred at room temperature for 30 hr. Brine was added to the reaction mixture, and the mixture was extracted twice with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate. The solvent was removed by distillation. The residue was purified by column chromatography on silica gel (dichloromethane:methanol=30:1) to give 156 mg of 3-azidomethylimidazo[5,1-b]thiazole.

NMR (CDCl 3 ): 4.49 (2H, s), 6.82 (1H, s), 7.15 (1H, s), 8.02 (1H, s).

b) 3-Azidomethyl-2-(tri-n-butystannyl)-imidazo[5,1-b]thiazole

In the same manner as in Preparation 16-d), 59.3 mg of the title compound was obtained from 69.3 mg of 3-azidomethylimidazo[5,1-b]thiazole.

NMR (CDCl 3 ): 0.92 (9H, t, J=7.3 Hz), 1.15-1.25 (6H, m), 1.25-1.4 (6H, m), 1.5-1.65 (6H, m), 4.41 (2H, s), 7.07 (1H, s), 7.96 (1H, s).

Preparation 42

3-t-Butyldimethylsilyloxymethyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

In the same manner as in Preparation 4-b), 3.92 g of the title compound was obtained from 2.68 g of 3-t-a butyldimethylsilyloxymethylimidazo[5,1-b]-thiazole.

NMR (CDCl 3 ): 0.15 (6H, s), 0.91 (9H, t, J=7.4 Hz), 0.93 (9H, s), 1.1-1.2 (6H, m), 1.3-1.4 (6H, m), 1.5-1.65 (6H, m), 4.68 (2H, s), 7.02 (1H, s), 8.02 (1H, s).

Preparation 43

3,7-Bis(methylthio)-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

a) 7-Methylthio-2-trimethylsily imidazo-[5,1-b]thiazole

A 1.59 N n-butyllithium/n-hexane solution (9.91 ml) was added dropwise in an argon atmosphere at −50° C. to a solution of 2.55 g of 7-methylthioimidazo[5,1-b]thiazole in 100 ml of THF. The mixture was stirred at the same temperature for 25 min. Trimethylsilyl chloride (2.08 ml) was added thereto, and the mixture was stirred for 30 min. The temperature of the system was raised to −30° C. A 1.59 N n-butyllithium/n-hexane solution (5.72 ml) was added dropwise thereto, and the mixture was stirred at the same temperature for 30 min. An aqueous ammonium chloride solution was added to the reaction solution. The mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and then filtered. The solvent was removed by distillation under the reduced pressure. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=1:2) to give 2.58 g of 7-methylthio-2-trimethylsilylimidazo[5,1-b]-thiazole.

›EXAMPLES · 16 of 19

NMR (CDCl 3 ): 0.34 (9H, s), 2.42 (3H, s), 7.27 (1H, s), 7.93 (1H, s).

b) 3,7-Bis(methylthio)-2-trimethylsilyl-imidazo[5,1-b]thiazole

A 1.59 N n-butyllithium/n-hexane solution (7.38 ml) was added dropwise in an argon atmosphere at −65° C. to a solution of 2.58 g of 7-methylthio-2-trimethylsilylimidazo[5,1-b]-thiazole in 40 ml of THF. The mixture was stirred at the same temperature for 20 min. Methylmethanethiol sulfonate (1.32 ml) was added thereto, and the mixture was stirred at −50° C. for 30 min. An aqueous ammonium chloride solution was added to the reaction solution. The mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and then filtered. The solvent was removed by distillation under the reduced pressure. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=1:1), to give 1.88 g of 3,7-bis(methylthio)-2-trimethylsilylimidazo[5,1-b]thiazole.

NMR (CDCl 3 ): 0.42 (9H, s), 2.39 (3H, s), 2.42 (3H, s), 8.02.(1H, s).

c) 3,7-Bis(methylthio[5,1-b]thiazole

A solution of 1.88 g of 3,7-bis(methylthio)-2-trimethylsilylimidazo[5,1-b]thiazole in 50 ml of THF was ice cooled. A 1 M tetra-n-butylammonium fluoride/THF solution (8.16 ml) was added in an argon atmosphere to the solution. The mixture was stirred at the same temperature for one hr. Brine was added thereto, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, and then filtered. The solvent was removed by distillation under the reduced pressure. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=1:1) to give 1.30 g of 3,7-bis(methylthio)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ): 2.44 (3H, s), 2.49 (3H, 5), 6.82 (1H, s), 8.04 (1H, s).

d) 3,7-Bis(methylthio)-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

In the same manner as in Preparation 4-b), 2.10 g of the title compound was obtained from 1.30 g of 3,7-bis(methylthio)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ): 0.92 (9H, t, J=7.3 Hz), 1.2-1.3 (6H, m), 1.3-1.4 (6H, m), 1.5-1.6 (6H, m), 2.37 (3H, s), 2.43 (3H, s), 7.99 (1H, s).

Preparation 44

7-(1-Propyl)thio-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

a) 1-Propyl 1-Propanethiolsulfonate

In the same manner as in Preparation 38-a), 666 mg of 1-propyl ,1-propanethiolsulfonate was obtained from 1.57 ml of dipropyl disulfide.

NMR (CDCl 3 ): 1.04 (3H, t, J=7.4 Hz), 1.09 (3H, t, J=7.4 Hz), 1.7-1.85 (2H, m), 1.9-2.05 (2H, m), 3.05-3.15 (2H, m), 3.25-3.35 (2H, m)

b) 7-(1-Propyl)thioimidazo[5,1-b]thiazole

In the same manner as in Preparation 38-b), 1.74 g of 7-(1-propyl)thioimidazo[5,1-b]thiazole was obtained from 3.33 g of 7-iodoimidazo[5,1-b]thiazole and 3.03 g of 1-propyl 1-propanesulfonate.

NMR (CDCl 3 ): 0.99 (3H, t, J=7.4 Hz), 1.55-1.7 (2H, m) 2.75-2.85 (2H, m), 6.86 (1H, d, J=4.2 Hz), 7.39 (1H, d, J=4.2 Hz), 8.00 (1H, s).

c) 7-(1-Propyl)thio-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

In the same manner as in Preparation 37-b), 1.84 g of the title compound was obtained from 882 mg of 7-(1-propyl)thioimidazo[5,1-b)]thiazole.

NMR (CDCl 3 ): 0.92 (9H, t, J=7.4 Hz), 0.99 (3H, t, J=7.4 Hz), 1.1-1.21 (6H, m), 1.3-1.4 (6H, m), 1.5-1.7 (8H, m), 2.7-2.8 (2H, m), 7.13 (1H, s), 7.94 (1H, s).

Preparation 45

7-Isopropylthio-2-(tri-n-butylstannyl)-imidazo[5,1-b]thiazole

7-Isopropylthioimidazo[5,1-b]thiazole

A 0.69 M isopropylmagnesium bromide/THF solution (9.13 ml) was added in an argon atmosphere under ice cooling to a solution of 1.50 g of 7-iodoimidazo[5,1-b]thiazole in 30 ml of dry THF. The mixture was then stirred at the same temperature for 20 min. Sulfur (211 mg) was added thereto, and the mixture was heated under reflux for one hr. A saturated aqueous ammonium chloride solution was added to the reaction mixture. The mixture was extracted twice with ethyl acetate, followed by washing with an aqueous sodium thiosulfate solution and a saturated brine in that order. The organic layer was dried over anhydrous magnesium sulfate. The solvent was removed by distillation. The residue was purified by column chromatography on silica gel(hexane:ethyl acetate=1:2) to give 833 mg of 7-isopropylthioimidazo[5,1-b]thiazole.

NMR (CDCl 3 ): 1.28 (6H, d, J=6.7 Hz), 3.28 (1H, sept, J=6.7 Hz), 6.87 (1H, d, J=4.2 Hz), 7.40 (1H, d, J=4.2 Hz), 8.02 (1H, s).

b) 7-Isopropylthio-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

In the same manner as in Preparation 4-b), 1.38 g of the title compound was obtained from 1.02 g of 7-isopropylthioimidazo[5,1-b]thiazole.

NMR (CDCl 3 ): 0.92 (9H, t, J=7.3 Hz), 1.1-1.2 (6H, m), 1.28 (6H, d, J=6.8 Hz), 1.3-1.14 (6H, m), 1.5-1.65 (6H, m), 3.26 (1H, sept, J=6.8 Hz), 7.14 (1H, s), 7.95 (1H, s).

Preparation 46

5-Methylthio-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

In substantially the same manner as in Preparation 12-a), 1.03 g of 5-methylthioimidazo[5,1-b]thiazole was obtained from 2.07 g of 5-iodoimidazo[5,1-b]thiazole.

NMR (CDCl 3 ): 2.52 (3H, s), 6.84 (1H, d, J=4.2 Hz), 7.13 (1H, s), 7.42 (1H, d, J=4.2 Hz).

b) 5-Methylthio-2-(tri-n-butylstannyl)-imidazo[5,1-b]thiazole

In substantially the same manner as in Preparation 4-b), 2.40 g of the title compound was obtained from 1.03 g of 5-methylthioimidazo[5,1-b])thiazole.

NMR (CDCl 3 ): 0.92 (9H, t, J=7.2 Hz), 1.16 (6H, m), 1.30-1.40 (6H, m), 1.55-1.64 (6H, m), 2.51 (3H, 5), 7.07 (1H, s), 7.15 (1H, s).

Preparation 47

5,7-Bis(methylthio-2-(tri-n-butylstannyl)-imidazo[5,1-b]thiazole

a) 5,7-Bis(methylthio)imidazo[5,1-b]thiazole

A 1 M ethylmagnesium bromide/THF solution (4.2 ml) was added in an argon atmosphere under ice cooling to a solution of 0.77 g of 5,7-diiodoimidazo[5,1-b]thiazole in 6 ml of dry THF. The mixture was stirred at the same temperature for one hr. Methylmethanethiol sulfonate (10.46 ml) was added thereto. The mixture was stirred at room temperature for 2 hr. A saturated aqueous ammonium chloride solution was added to the reaction mixture. Ethyl acetate was then added thereto, followed by washing with a dilute aqueous sodium thiosulfate solution and a saturated brine in that order. The organic layer was dried over anhydrous magnesium sulfate. The solvent was removed by distillation. The residue was purified by column chromatography on silica gel (ethyl acetate:hexane=1:2) to give 0.27 g of 5,7-bis(methylthio)imidazo[5,1-b]thiazole.

›EXAMPLES · 17 of 19

NMR (CDCl 3 ): 2.43 (3H, s), 2.55 (3H, s), 6.86 (1H, d, J=4.4 Hz), 7.38 (1H, d, J=4.4 Hz).

b) 5,7-Bis(methylthio)-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

In substantially the same manner as in Preparation 4-b), 2.31 g of the title compound was obtained from 1.66 g of 5,7-bis(methylthio)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ): 0.92 (9H, t, J=7.2 Hz), 1.17 (6H, m), 1.31-1.41 (6H, m), 1.55-1.64 (6H, m), 2.42 (3H, s), 2.54 (3H, s), 7.12 (1H, s).

Preparation 48

3-Methylthio-2-(tri-n-butylstannyl)imidazo-[5,1-b]thiazole

a) 2-(Trimethylsilyl)imidazo[5,1-b]thiazole

A 1.6 N n-butyllithium/n-hexane, solution (16.7 ml) was added in an argon atmosphere at −50° C. to a solution of 3.17 g of imidazo[5,1-b]thiazole in 120 ml of dry THF. The mixture was stirred at the same temperature for 30 min. Trimethylsilyl chloride (3.54 ml) was added thereto, and the mixture was stirred for 20 min. A 1.6 N n-butyllithium/n-hexane solution (8.0 ml) was added thereto, and the mixture was stirred for 20 min. A saturated aqueous ammonium chloride solution was added to the reaction mixture. Ethyl acetate was then added thereto, followed by washing with water and saturated brine in that order. The organic layer was dried over anhydrous magnesium sulfate. The solvent was removed by distillation. The residue was purified by column chromatography on silica gel (ethyl acetate) to give 4.53 g of 2-(trimethylsilyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ): 0.34 (9H, s), 7.04 (1H, s), 7.29 (1H, s), 7.94 (1H, s).

b) 3-Methylthio-2-(trimethylsilyl)imidazo-[5,1-b]thiazole

A 1.6 N n-butyllithium/n-hexane solution (15.3 ml) was added in an argon atmosphere at −55° C. to a solution of 4.40 g of 2-(trimethylsilyl)imidazo[5,1-b]thiazole in 70 ml of dry THF. The mixture was stirred at the same temperature for 30 min. Methylmethanethiol sulfonate (2.75 ml) was then added thereto. The temperature of the system was raised to −5° C. over a period of 2 hr. A saturated aqueous ammonium chloride solution was added to the reaction mixture. Ethyl acetate was then added thereto, followed by washing with water and saturated brine in that order. The organic layer was dried over anhydrous magnesium sulfate. The solvent was removed by distillation. The residue was purified by column chromatography on silica gel (ethyl acetate) to give 3.87 g of 3-methylthio-2-(trimethylsilyl)imidazo[5,1-b]-thiazole.

NMR (CDCl 3 ): 0.41 (9H, s), 2.39 (3H, s), 7.10 (1H, s), 8.04 (1H, s).

c) 3-Methylthioimidazo[5,1-b]thiazole

A 1 M Tetra-n-butylammonium fluoride/THF solution (20.0 ml) was added in an argon atmosphere at room temperature to a solution of 3.87 g of 3-methylthio-2-(trimethylsilyl)imidazo[5,1-b]-thiazole in 70 ml of dry THF. The mixture was stirred at the same temperature for 15 min. Semi-saturated brine was added to the reaction mixture. Ethyl acetate was then added thereto, followed by washing with semi-saturated brine. The organic layer was dried over anhydrous magnesium sulfate. The solvent was removed by distillation. The residue was purified by column chromatography on silica gel (ethyl acetate) to give 2.62 g of 3-methylthioimidazo[5,1-b]thiazole.

NMR (CDCl 3 ): 2.49 (3H, s), 6.80 (1H, s), 7.14 (1H, s), 8.05 (1H, s).

d) 3-Methylthio-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

In substantially the same manner as in Preparation 4-b), 5.44 g of the title compound was obtained from 2.62 g of 3-methylthioimidazo[5,1-b]thiazole.

NMR (CDCl 3 ): 0.92 (9H, t, J=7.3 Hz), 1.24 (6H, m), 1.30-1.40 (6H, m), 1.54-1.63 (6H, m), 2.37 (3H, s), 7.14 (1H, s), 8.01 (1H, s).

Preparation 49

5-Acetyl-7-methylthio-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

a) 5-Iodo-7-methylthioimidazo[5,1-b]thiazole

N-Iodosuccinimide (3.08 g) was added under ice cooling to a solution of 2.28 g of 7-methylthioimidazo[5,1-b]thiazole in dichloromethane. The mixture was stirred at room temperature for 7 hr. Saturated brine was added to the reaction mixture, followed by separation. The organic layer was washed with a dilute aqueous sodium thiosulfate solution and saturated brine in that order, and then dried over anhydrous magnesium sulfate. The solvent was removed by distillation. The residue was purified by column chromatography on silica gel (ethyl acetate:dichloromethane=1:1) to give 3.78 g of 5-iodo-7-methylthioimidazo[5,1-b]thiazole.

NMR (CDCl 3 ): 2.42 (3H, s), 6.93 (1H, d, J=4.4 Hz), 57.25 (1H, d, J=4.4 Hz).

b) 5-Acetyl-7-methylthioimidazo[5,1-b]-thiazole

A 1 M ethylmagnesium bromide/THF solution (4.78 ml) was added in an argon atmosphere at −40° C. to a solution of 963 mg of 5-iodo-7-methylthioimidazo[5,1-b]thiazole in 30 ml of dry THF. The mixture was stirred at the same temperature for 30 min. Acetyl chloride (0.35 ml) was added thereto. The temperature of the system was raised to −5° C. over a period of 2 hr. A saturated aqueous ammonium chloride solution was added to the reaction mixture. Ethyl acetate was added thereto, followed by washing with a dilute aqueous sodium thiosulfate solution and saturated brine in that order. The organic layer was dried over anhydrous magnesium sulfate. The solvent was removed by distillation. The residue was purified by column chromatography on silica gel (dichloromethane:ethyl acetate:hexane=2:1:1) to give 384 mg of 5-acetyl-7-methylthioimidazo[5,1-b]thiazole.

NMR (CDCl 3 ): 2.52 (3H, s), 2.67 (3H, s), 7.10 (1H, d, J=4.2 Hz), 8.46 (1H, d, J=4.2 Hz)

c) 5-Acetyl-7-methylthio-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

In substantially the same manner as in Preparation 5-b), 283 mg of the title compound was obtained from 378 mg of 5-acetyl-7-methylthioimidazo[5,1-b]thiazole.

NMR (CDCl 3 ): 0.92 (9H, t, J=7.3 Hz), 1.19 (6H, m), 1.33-1.44 (6H, m), 1.55-1.64 (6H, m), 2.52 (3H, s), 2.66 (3H, s), 8.23 (1H, s).

Preparation 50

5-Cyano-7-methylthio-2-(tri-n-butylstannyl)-imidazo[5,1-b]thiazole

a) 5-Cyano-7-methylthioimidazo[5,1-b]thiazole

A 1 M ethylmagnesium bromide/THF solution (2.0 ml) was added in an argon atmosphere at −40° C. to a solution of 405 mg of 5-iodo-7-methylthioimidazo[5,1-b]thiazole in 12 ml of dry THF. The mixture was stirred at the same temperature for 30 min. p-Toluenesulfonyl cyanide (372 mg) was added thereto. The temperature of the system was raised to −5° C. over a period of one hr. A saturated aqueous ammonium chloride solution was added to the reaction mixture. Ethyl acetate was added thereto, followed by washing with saturated brine. The organic layer was dried over anhydrous magnesium sulfate. The solvent was removed by distillation. The residue was purified by column chromatography on silica gel (dichloromethane:ethyl acetate:hexane=3:1:1) to give 131 mg of 5-cyano-7-methylthioimidazo[5,1-b]thiazole.

›EXAMPLES · 18 of 19

NMR (CDCl 3 ): 2.52 (3H, s), 2.67 (3H, s), 7.10 (1H, d, J=4.2 Hz), 8.46 (1H, d, J=4.2 Hz),

b) 5-Cyano-7-methylthio-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

In substantially the same manner as in Preparation 4-b), 262 mg of the title compound was obtained from 253 mg of 5-cyano-7-methylthio-imidazo[5,1-b]thiazole.

NMR (CDCl 3 ): 0.93 (9H, t, J=7.3 Hz), 1.23 (6H, m), 1.31-1.41 (6H, m), 1.52-1.62 (6H, m), 2.50 (3H, s), 7.37 (1H, s).

Preparation 51

7-(4-Nitrobenzyloxycarbonylamino)acetyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

a) 7-(4-Nitrobenzyloxycarbonylamino)acetylimidazo[5,1-b]thiazole

7-Azidoacetylimidazo[5,1-b]thiazole (1.71 g) was dissolved in 60 ml of THF. Water (30 ml), 24.8 ml of 1 N hydrochloric acid, and 850 mg of 10%Pd—C were added to the solution. A reaction was allowed to proceed in a hydrogen atmosphere at room temperature for one hr. After the completion of the reaction, the catalyst was removed by filtration through Celite, followed by washing with a 50% aqueous THF solution. A 1 N aqueous sodium hydroxide solution (34.7 ml,) and 2.14 g of 4-nitrobenzyl chlorocarbonate were added under ice cooling to the filtrate. The mixture was allowed to react at the same temperature for one hr. The resultant precipitate was collected by filtration, washed with a 50% aqueous THF solution (20 ml) and ethyl acetate (20 ml) in that order, land then dried under the reduced pressure to, give 2.59 g of 7-(4-nitrobenzyloxycarbonylamino)acetylimidazo-[5,1-b]thiazole.

NMR (DMSO-d 6 ): 4.47 (2H, d), 5.52 (2H, s), 7.53 (1H, d), 7.65 (2H, d), 8.10 (1H, d), 8.26 (2H, d), 8.35 (1H, s).

b) 7-(4-Nitrobenzyloxycarbonylamino)acetyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

7-(4-Nitrobenzyloxycarbonylamino)acetylimidazo[5,1-b]thiazole (2.52 g) was suspended in 50 ml of anhydrous THF. The suspension, was cooled in an argon atmosphere to −70° C. Tri-n-butylstannyl chloride (3 ml) was added to the suspension. A solution (31.5 ml) of 1 N lithiumbis(trimethylsilyl)amide in THF was then added dropwise thereto over a period of 20 min. The mixture was allowed to react at the same temperature for one hr. The reaction solution was poured into a mixed solution composed of 250 ml of ethyl acetate and 150 ml of 15% brine. The organic layer was washed with 15% brine, and then dried over anhydrous magnesium sulfate. The solvent was removed by distillation. The residue was purified by column chromatography on silica gel (ethyl acetate:dichloromethane=1:10) to give 1.41 g of the title compound.

NMR (CDCl 3 ): 0.92 (9H, t), 1.21 (6H, m), 1.38 (6H, m), 1.58 (6H, m), 4.77 (2H, d), 5.26 (2H, s), 5.88 (1H, m), 7.30 (1H, s), 7.54 (2H, d), 7.95 (1H, s), 8.22 (2H, d).

Preparation 52

7-(4-Nitrobenzyloxycarbonylaminomethyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

a) 7-(4-Nitrobenzyloxycarbonylamino)methyl-imidazo[5,1-b]thiazole

7-Aminomethylimidazo[5,1-b]thiazole (1.53 g) was dissolved in 50 ml of THF and 30 ml of water. A 1 N aqueous sodium hydroxide solution (12 ml) and 2.59 g of 4-nitrobenzyl chlorocarbonate were added under ice cooling to the solution. The mixture was allowed to react at the same temperature for 30 min. The reaction solution was extracted with 200 ml of ethyl acetate, followed by washing with 15% brine. The organic layer was dried over anhydrous magnesium sulfate, and concentrated under the reduced pressure to about 20 ml. The resultant crystal.was collected by filtration, washed with 20 ml of ethyl acetate, and dried under the reduced pressure to give 2.26 g of 7-(4-nitrobenzyloxycarbonylamino)methylimidazo-[5,1-b]thiazole.

NMR (DMSO-d 6 ): 4.23 (2H, d), 5.21 (2H, s), 7.14 (1H, d), 7.62 (2H, d), 7.81 (1H, d), 7.96 (1H, m), 8.10 (1H, s), 8.24 (2H, d).

b) 7-(4-Nitrobenzyloxycarbonylamino)methyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

The title compound (772 mg) was obtained from 1.59 g of 7-(4-nitrobenzyloxycarbonylamino)methyl-imidazo[5,1-b]thiazole in the same manner as in Preparation 51-b), except that a mixed solution of anhydrous THF-HMPA was used as the reaction solvent.

NMR (CDCl 3 ): 0.91 (9H, t), 1.15 (6H, m), 1.35 (6H, m), 1.58 (6H, m), 4.47 (2H, d), 5.22 (2H, s), 5.42 (1H, m), 7.12 (1H, s), 7.52 (2H, d), 7.89 (1H, s), 8.20 (2H, d).

Preparation 53

3-Phenyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

In the same manner as in Preparation 4-b), 1.09 g of the title compound was obtained from 600 mg of 3-phenylimidazo[5,1-b]thiazole.

NMR (CDCl 3 ): 0.85 (9H, t), 0.92 (6H, m), 1.25 (6H, m), 1.40 (6H, m), 7.06 (1H, s), 7.50 (5H, s), 7.77 (1H, s).

Preparation 54

7-((E)-3-Oxo-1-buten-1-yl)-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

a) 7-((E)-3-Oxo-1-buten-1-yl)imidazo[5,1-b]-thiazole

7-Formyl-imidazo[5,1-b]thiazole was dissolved in 15 ml of methanol. Methyl (triphenylphosphoranylidene)acetate (500 mg) was added to the solution. The mixture was stirred at room temperature for 15 min. The reaction solution was concentrated under the reduced pressure. The concentrate was purified by chromatography on silica gel to give 208 mg of 7-((E)-3-Oxo-1-buten-1-yl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ): 2.39 (3H, s), 6.43 (1H, dd, J=16.3 Hz), 7.04 (1H, d, J=4.1 Hz), 7.52 (1H, d, J=16.3 Hz), 8.09 (1H, s).

b) 7-((E)-3-Oxo-1-buten-1-yl)-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

In the same manner as in Preparation 4-b), 408 mg of the title compound was obtained from 208 mg of 7-((E)-3-oxo-buten-1-yl)imidazo[5,1-b]-thiazole

NMR (CDCl 3 ): 0.94 (9H, t, J,=7.3 Hz), 1.15-1.40 (12H, m), 1.55-1.65 (6H, m), 2.37 (3H, s), 6.38 (1H, d, J=16.1 Hz), 7.25 (1H, s), 7.65 (1H, d, J=16.1 Hz), 8.02 (1H, s).

Preparation 55

7-(t-Butyldimethylsiloxy)methyl-5-methyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

a) 7-formyl-5-methylimidazo[5,1-b]thiazole

DMF (8 ml) was added to 40 ml of dichloromethane. The mixture was cooled in an argon atmosphere to 0° C. A solution of 9 ml of phosphorus oxychloride in 40 ml of dichloromethane was added dropwise thereto. Further, a solution of 1.2 g of 5-methylimidazo[5,1-b]thiazole in 20 ml of dichloromethane was added dropwise thereto. The mixture was heated under reflux for 5 hr. The reaction solution was poured into iced water, and then adjusted to pH 10 by the addition of an aqueous sodium hydroxide solution. The mixture was extracted with dichloromethane. The extract was dried over magnesium sulfate. The solvent was then concentrated under the reduced pressure. The residue was purified by chromatography on silica gel to give 1.5 g of 7-formyl-5-methylimidazo[5,1-b]thiazole.

›EXAMPLES · 19 of 19

NMR (CDCl 3 ): 2.26 (3H, s), 7.13 (1H, d, J=4.1 Hz), 7.42 (1H, d, J=4.1 Hz), 9.84 (1H, s)

b) 7-(t-Butyldimethylsilyloxy)methyl-5-methylimidazo[5,1-b]thiazole

7-Formyl-5-methylimidazo[5,1-b]thiazole (1.5 g) was dissolved in 20 ml of methanol. Sodium boronhydride(210 mg) was added to the solution. The mixture was stirred at 0° C. for 40 min. A saturated sodium hydrogencarbonate solution was added thereto. The mixture was extracted with dichloromethane. The extract was dried over magnesium sulfate, and then concentrated under the reduced pressure. The residue was dissolved in DMF. Imidazole (900 mg) and 1.8 g of t-butyldimethylsilyl chloride were added in an argon atmosphere to the solution. The mixture was stirred at room temperature for 16 hr. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate, followed by washing with saturated brine. The extract was dried over magnesium sulfate. The solvent was removed under the reduced pressure. The residue was purified by chromatography on silica gel to give 2.18 g of 7-(t-butyldimethylsilyloxy)methyl-5-methylimidazo-[5,1-b]thiazole.

NMR (CDCl 3 ): 0.13 (6H, s), 0.98 (99H, s), 2.54 (3H, s), 4.84 (2H, s), 6.73 (1H, d, J=4.4 Hz) 7.16 (1H, d, J=4.4 Hz), 7.27 (1H, s).

c) 7-(t-Butyldimethylsilyloxy)methyl-5-methyl-2-(tri-n-butylstannyl)imidazo[5,1-b]-thiazole

In the same manner as in Preparation 4-b), 1.2 g of the tile compound was obtained from 980 mg of 7-(t-butyldimethylsilyloxy)methyl-5-methyl-imidazo[5,1-b]thiazole.

NMR (CDCl 3 ): 0.13 (6H, s), 0.93 (9H, t, J=7.3 Hz), 0.97 (9H, s), 1.13 (6H, s), 1.36 (6H, s), 1.58 (6H, s), 2.53 (3H, s), 4.82 (2H, s), 6.88 (1H, s), 7.27 (1H, s).

›Examples225

›Example 1

Sodium (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-1-methyl-2-(7-propionylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-1-methyl-2-(7-propionylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

N,N-Diisopropylethylamine (0.392 ml) and 0.252 ml of trifluoromethanesulfonic anhydride were added dropwise in that order to a solution of 543 mg of 4-nitrobenzyl (1R, 3R, 5R, 6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-oxo-1-carbapenam-3-carboxylate in 15 ml of dry acetonitrile in an argon atmosphere at −30° C. The mixture was stirred at that temperature for 30 min. Ethyl acetate (150 ml) was added thereto. The mixture was then washed with semisaturated brine, a mixed solution (pH 1.1) composed of semisaturated brine and a 1 N aqueous hydrochloric acid solution, a mixed solution, (pH 8.9) composed of semisaturated brine and a saturated aqueous sodium hydrogencarbonate solution, and semisaturated brine in that order. The mixture was then dried over anhydrous magnesium sulfate and filtered. The solvent was removed by distillation under the reduced pressure. The residue was dissolved in 8 ml of dry N-methylpyrrolidinone. Tri-2 furylphosphine (42 mg), 409 mg of zinc chloride, 42 mg of tris(dibenzylideneacetone) dipalladium (0), and 844 mg of 7-propionyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole were added to the solution. The mixture was stirred in an argon atmosphere at 50° C. for 1.5 hr. Ethyl acetate (106 ml) and 50 ml of a semisaturated aqueous sodium hydrogencarbonate solution were added to the reaction solution, followed by stirring. The insolubles were removed by filtration. The organic layer was separated from the filtrate, washed three times with 100 ml of semisaturated brine, and dried over anhydrous magnesium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by column chromatography on silica gel (dichlorombethane:methanol=30:1 to 20:1) to give 454 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-proponylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate.

NMR (CDCl 3 ) δ: 1.26 (3H, t, J=7.4 Hz), 1.30 (3H, d, J=7.4 Hz), 1.60 (3H, d, J=6.3 Hz), 3.06 (2H, q, J=7.4 Hz), 3.39 (1H, dd, J 1 =6.4 Hz, J 2 =2.8 Hz), 3.52 (1H, m), 4.33(1H, m), 4.41 (1H, dd, J 1 =9.8 Hz, J 2 =2.8 Hz), 5.28 (1H, d, J=13.5 Hz), 5.52 (1H, d, J=13.5 Hz), 7.68 (2H, d, J=8.9 Hz), 8.00 (1H, s), 8.24 (2H, d, J=8.9 Hz), 8.51 (1H, s).

b) Sodium (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-1-methyl-2-(7-propionylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

4-Nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-propionylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (350 mg) was dissolved in 20 ml of THF and 20 ml of 1/15 M sodium phosphate buffer (pH 6.6). 10%Pd—C (350 mg) was added to the solution. The atmosphere in the reactor was replaced by hydrogen, and the system was stirred at room temperature for 1.5 hr. The catalyst was removed by filtration through Celite, followed by washing with water. The filtrate was adjusted to pH 7.0 by the addition of an aqueous sodium hydrogencarbonate solution, and washed with ethyl acetate. The aqueous layer was purified by column chromatography on Diaion HP-20 (10% aqueous methanol) to give 198 mg of the title compound.

NMR (D 2 O) δ (HOD=4.80 ppm): 1.18 (3H, t, J=7.5 Hz), 1.25 (3H, d, J=7.1 Hz), 1.33 (3H, d, J=6.3 Hz), 2.93 (2H, q, J=7.5 Hz), 3.53 (1H, m), 3.64 (1H, m), 4.31 (2H, m), 8.04 (1H, s), 8.17(1H, s).

›Example 2

Pivaloyloxymethyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-1-methyl-2-(7-propionylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

Sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-propionylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (75.8 mg) was dissolved in 7 ml of DMF.

Sodium hydrogencarbonate (4.9 mg) and 0.038 ml of pivaloyloxymethyl iodide were added to the solution in an argon atmosphere at −30° C. The mixture was stirred for 1.5 hr. Ethyl acetate (50 ml) was added to the reaction solution. The mixture was washed three times with 30 ml of semisaturated brine. The organic layer was dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated to 5 ml under the reduced pressure. The residue was purified by column chromatography on silica gel (dichloromethane:methanol=30:1) to give 62.3 mg of the title compound.

NMR (CDCl 3 ) δ: 1.20 (9H, s), 1.26 (3H, t, J=7.4 Hz), 1.28 (3H, d, J=7.2 Hz), 1.37 (3H, d, J=6.3 Hz), 3.07 (2H, q, J=7.4 Hz), 3.35 (1H, dd, J 1 =6.6 Hz, J 2 =2.8 Hz), 3.50 (1H, m), 4.30 (1H, m), 4.39 (1H, dd, J=9.6 Hz, J 2 =2.8 Hz), 5.87 (1H, d, J=5.6 Hz), 5.99 (1H, d, J=5.6 Hz), 8.03 (1H, s), 8.51 (1H, s).

›Example 3

Sodium (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-hydroxyiminomethylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Geometrical Isomer Derived From a Starting Compound as a Low-polarity Oxime Isomer)

a) 4-Nitrobenzyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-1-methyl-2-[7-(4-nitrobenzyloxyiminomethyl)imidazo[5,1-b]thiazol-2-yl-1-carbapen-2-em-3-carboxylate (a Geometrical Isomer Derived From a Starting Compound as a Low-polarity Oxime Isomer)

In the same manner as in Example 1-a), 77.3 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-[7-(4-nitrobenzyloxyiminomethyl)imidazo[5,1-b]thiazol-2-yl]-1-carbapen-2-em-3-carboxylate (a geometrical isomer derived from a starting compound as a low-polarity oxime isomer) was obtained from 86 mg of 4-nitrobenzyl (1R,3R,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-oxo-1-carbapenam-3-carboxylate and 169 mg of 7-(4-nitrobenzyloxyiminomethyl)-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole (a geometrical isomer derived from a starting compound as a low-polarity oxime isomer).

NMR (DMSO-d 6 ) δ: 1.20 (6H, m), 3.42 (1H, m), 3.70 (1H, m), 4.03 (1H, m), 4.34 (1H, m), 5.26 (2H, s), 5.39 (1H, d, J=13.5 Hz), 5.53 (1H, d, J=13.5 Hz), 7.71 (4H, m), 8.22 (4H, m), 8.32 (2H, s), 8.50 (1H, s).

b) Sodium (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-hydroxyiminomethylimidazo[5,1-b]thiazol-2-yl)-1-methyl-carbapen-2-em-3-carboxylate (a Geometrical Isomer Derived From a Starting Compound as a Low-polarity Oxime Isomer)

The title compound (2.4 mg) was obtained from 77.3 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-[7-(4-nitrobenzyloxyiminomethyl)imidazo[5,1-b]-thiazol-2-yl]-1-carbapen-2-em-3-carboxylate (a geometrical isomer derived from a starting compound as a low-polarity oxime isomer) in the same manner as in Example 1-b), except that the purification was carried out by column chromatography on Diaion HP-20 (10% aqueous methanol) and Cosinosil 40C18-PREP (20% aqueous methanol).

NMR (D 2 O) δ (HOD=4.80 ppm): 1.22 (3H, d, J=6.6 Hz), 1.31 (3H, d, J=6.3 Hz), 3.50 (2H, m), 4.28 (2H, m), 7.84 (1H, s), 8.04 (1H,s ) 8.17 (1H, s).

›Example 4

Sodium (5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methoxyiminomethylimidazo[5,1-b]thiazol-3-yl)-1-carbapen-2-em-3-carboxylate (a Geometrical Isomer Derived From a Starting Compound as a Low-polarity Oxime Isomer)

a) 4-Nitrobenzyl (5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methoxyiminomethylimidazo[5,1-b]thiazol-3-yl)-1-carbapen-2-em-3-carboxylate (a Geometrical Isomer Derived From a Starting Compound as a Low-polarity Oxime Isomer)

In the same manner as in Example 1-a), 357 mg of 4-nitrobenzyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methoxyiminomethylimidazo[5,1-b]thiazol-3-yl)-1-carbapen-2-em-3-carboxylate (a geometrical isomer derived from a starting compound as a low-polarity oxime isomer) was obtained from 522 mg of 4-nitrobenzyl (3R,5R,6S)-6-((1R)-1-hydroxyethyl)-2-oxo-1-carbapenam-3-carboxylate and 846 mg of 7-methoxyiminomethyl-3-(tri-n-butylstannyl)imidazo[5,1-b]thiazole (a geometrical isomer derived from a starting compound as a low-polarity oxime isomer).

NMR (CDCl 3 ) δ: 1.40 (3H, d, J=6.3 Hz), 3.39 (3H, m), 3.96 (3H, s), 4.32 (1H, m), 4.45 (1H, m), 5.17 (1H, d, J=13.3 Hz), 5.32 (1H, d, J=13.3 Hz), 7.15 (1H, s), 7.37 (2H, d, J=8.5 Hz), 7.74 (1H, s), 8.15 (1H, s), 8.15 (2H, d, J=8.5 Hz).

b) Sodium (5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methoxyiminomethylimidazo[5,1-b]thiazol-3-yl)-1-carbapen-2-em-3-carboxylate (a Geometrical Isomer Derived From a Starting Compound as a Low-polarity Oxime Isomer)

The title compound (93.9 mg) was obtained from 287 mg of 4-nitrobenzyl (5R, 6S)-6-((1R)-1-hydroxyethyl)-2-(7-methoxyiminomethylimidazo[5,1-b]thiazol-3-yl)-1-carbapen-2-em-3-carboxylate (a geometrical isomer derived from a starting compound as a low-polarity oxime isomer) in the same manner as in Example 1-b), except that the purification was carried out by column chromatography on Diaion HP-20 (10% aqueous methanol) and Cosmosil 40C18-PREP (10% aqueous methanol).

NMR (D 2 O) δ (HOD=4.80 ppm): 1.32 (3H, d, J=6.3 Hz), 3.21 (1H, m), 3.48 (1H, m), 3.60 (1H, n), 3.94 (3H, s), 4.28 (1H, m), 4.39 (1H, m), 7.20 (1H, s), 7.94 (1H, 3), 8.22 (1H, s).

›Example 5

Pivaloyloxymethyl (5R,6S)-6-((R)-1-Hydroxyethyl)-2(7-methoxyiminomethylimidazo[5,1-b]thiazol-3-yl)-1-carbapen-2-em-3-carboxylate (a Geometrical Isomer Derived From a Starting Compound as a Low-polarity Oxime Isomer)

In the same manner as in Example 2, 22.6 g of the title compound was obtained from 40.0 mg of sodium (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methoxyiminomethylimidazo-[5,1-b]thiazol-3-yl)-1-carbapen-2-em-3-carboxylate (a geometrical isomer derived from a starting compound as a low polarity oxime isomer).

NMR (CDCl 3 ) δ: 1.19 (9H, s), 1.38 (3H, d, J=6.3 Hz), 73.3 (3H, m), 3.96 (3H, s), 4.30 (1H, m), 4.42 (1H, m), 5.78 (1H,d, J=5.6 Hz), 5.88 (1H, d, J=5.6 Hz), 7.25 (1H, s), 7.79 (1H, s), 8.21 (1H, s).

›Example 6

Sodium (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-1-methyl-2-(7-pivaloylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-1-methyl-2-(7-pivaloylimidazo[5,1-b]-thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

In substantially the same manner as in Example 1-a), 487 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-pivaloylimidazo[5,1-b]-thiazol-2-yl)-1-carbapen-2-em-3-carboxylate was obtained from 362 mg of 4-nitrobenzyl (1R,3R,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-oxo-1-carbapenam-3-carboxylate and 460 mg of i7-pivaloyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (DMSO-d 6 ) δ: 1.22 (3H, t, J=7.4 Hz), 1.30 (12H, m), 3.38-3.43 (1H, m), 3.60-3.70 (11H, m), 3.95-4.05 (1H, m), 4.27-4.32 (1H, m), 5.38 (1H, d, J=13.5 Hz), 5.50 (1H, d, J=13.5 Hz), 7.71 (2H, d, J=8.9 Hz), 8.20-8.30 (3H, m), 8.35 (1H, s).

b) Sodium (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-1-methyl-2-(7-pivaloylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate The title compound (99 mg) was obtained from 487 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-pivaloylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate in substantially the same manner as in Example 1-b), except that the purification was carried out using Cosmosil 40C18-PREP (10% aqueous acetonitrile).

NMR (D 2 O) δ (HOD=4.80 ppm): 1.24 (3H, d, J=7.1 Hz), 1.28.-1.32 (12H, m), 3.46-454 (2H, m), 4.23-4.32 (2H, m), 7.81 (1H, s), 8.02 (1H, s).

›Example 7

Pivaloyloxymethyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-1-methyl-2-(7-pivaloylimidazo[5,1-b]-thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

In substantially the same manner as in Example 2, the title compound (31 mg) was obtained from 40 mg of sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-pivaloylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate.

NMR (CDCl 3 ) δ: 1.22 (9H, s), 1.28 (3H, d, J=7.3 Hz), 1.35-1.40 (12H, m), 3.31 (1H, dd, J 1 =6.7 Hz, J 2 =2.8 Hz), 3.40-3.56 (1H, m), 5.88 (1H, d, J=5.6 Hz), 5.98 (1H, d, J=5.6 Hz), 7.89 (1H, s), 18.25 (1H, s).

›Example 8

Sodium (5R,6S)-2-(7-Acetyl-3-methylimidazo[5,1]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (5R,6S)-2-(7-Acetyl-3-methylimidazo[5,1-b]thiazol-2-yl)-6-1-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 303 mg of 4-nitrobenzyl (5R,6S)-2-(7-acetyl-3-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate was obtained from 453 mg of 4-nitrobenzyl (3R,5R,6S)-6-((1R)-1-1-hydroxyethyl)-2-oxo-1-carbapenam-3-carboxylate and 745 mg of 7-acetyl-3-methyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 1.40 (3H, d, J=6.3 Hz), 2.27 (3H, s), 2.61 (3H, s), 3.21 (1H, dd, J 1 =18.5 Hz, J 2 =9.4 Hz), 3.23 (1H, dd, J 1 =18.5 Hz, J 2 =9.5 Hz), 3.38 (1H, dd, J 1 =6.4 Hz, J 2 =3.0 Hz), 4.26-4.41 (1H, m), 4.42 (1H, td, J 1 =9.5 Hz J 2 =3.0 Hz), 5.23 (1H, d, J=13.5 Hz), 5.41 (1H, d, J=13.5 Hz), 7.55 (2H, dm, J=8.8 Hz), 7.82 (1H, s), 8.16 (2H, dm, J=8.8 Hz)

b) Sodium (5R,6S)-2-(7-Acetyl-3-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-b), the title compound (125 mg) was obtained from 303 mg of 4-nitrobenzyl (5R,6S)-2-(7-acetyl-3-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate.

NMR (D 2 O) δ (HOD=4.80 ppm): 1.30 (3H, d, J=6.5 Hz), 2.35 (3H, s), 2.54 (3H, s), 3.14 (1H, dd, J 1 =17.3 Hz, J 2 =9.9 Hz), 3.33 (1H, dd, J 1 =17.3 Hz, J 2 =8.4 Hz), 3.57 (1H, dd, J 1 =5.8 Hz, J 2 =3.1 Hz), 4.27 (1H, qd, J 1 =6.5 Hz, J 2 =5.8 Hz), 4.36 (1H, ddd, J 1 =9.9 Hz, J 2 =8.4 Hz), J 3 =3.1 Hz), 8.19 (1H, s).

›Example 9

Pivaloyloxymethyl (5R,6S)-2-(7-Acetyl-3-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 2, the title compound (19 mg) was obtained from 35 mg of sodium (5R,6S)-2-(7-acetyl-3-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate.

NMR (CDCl 3 ) δ: 1.10 (9H, s), 1.37 (3H, d, J=6.3 Hz), 1.99 (1H, broad), 2.37 (1H, s), 2.61 (1H, s), 3.20 (1H, dd, J 1 =18.5 Hz, J 2 =7.5 Hz), 3.22 (1H, dd, J 1 =18.5 Hz, J 2 =7.5 Hz), 3.35 (1H, dd, J 1 =6.5 Hz, J 2 =3.0 Hz), 4.33 to 4.35 (1H, m), 4.39 (1H, td, J 1 =9.5 Hz, J 2 =3.0 Hz), 5.78 (1H, d, J=5.5 Hz), 5.88 (1H, d, J=5.5 Hz), 7.90 (1H, s).

›Example 10

Sodium (1S,5R,6S)-2-[7-(2-Formylaminopropionyl)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a High-polarity Isomer)

In substantially the same manner as in Example 1-a), 68 mg of a crude product of 4-nitrobenzyl (1S,5R,6S)-2-[7-(2-formylaminopropionyl)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers) was obtained from 91 mg of 4-nitrobenzyl (1R,3R,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-oxo-1-carbapenam-3-carboxylate and 96 mg of 7-(2-formylaminopropionyl)-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole. The title compound (3.2 mg) was obtained from this crude product in substantially the same manner as in Example 6-b).

NMR (D 2 O) δ (HOD=4.80 ppm): 1.23 (3H, d, J=7.1 Hz), 1.32 (3H, d, J=6.3 Hz), 1.50 (3H, d, J=7.4 Hz), 3.52 (1H, dd, J 1 =6.1 Hz, J 2 =2.1 Hz), 3.55-3.65 (1H, m), 4.22-4.35 (2H, m), 5.35 (1H, q, J=7.4 Hz), 8.0 (1H, s), 8.12 (2H, m).

›Example 11

Sodium (1S,5R,6S)-2-[7-(2-Formylaminopropionyl)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Low-polarity Isomer)

In substantially the same manner as in Example 6-b), the title compound (3.4 mg) was obtained from 68 mg of the crude product of 4-nitrobenzyl (1S,5R,6S)-2-[7-(2-formylaminopropionyl)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers) prepared in Example 10.

NMR (D 2 O) δ (HOD=4.80 ppm): 1.23 (3H, d, J=7.1 Hz), 1.32 (3H, d, J=6.3 Hz), 1.47 (3H, d, J=7.4 Hz), 3.50 (1H, dd, J 1 =6.0 Hz, J 2 =2.4 Hz), 3.55-3.65 (1H, m), 4.23-4.35 (2H, m), 5.32 (1H, d, J=7.4 Hz), 8.03 (1H, s), 8.13 (1H, s), 8.18 (1H, s)

›Example 12

Sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-isobutyrylimidazo[5,1-b]thiazol-2-yl) 1-methyl-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-isobutyrylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 440 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-isobutyrylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate was obtained from 725 mg of 4-nitrobenzyl (1R,3R,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-oxo-1-carbapenam-3-carboxylate and 1.03 g of 7-isobutyryl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 1.13 (6H, d, J=6.6 Hz), 1.20 (3H, d, J=7.4 Hz), 1.29 (3H, d, J=6.0 Hz), 3.30 (1H, m), 3.46 (1H, m), 3.58 (1H, m), 4.19 (1H, m), 4.36 (1H, dd, J 1 =9.6 Hz, J 2 =2.7Hz), 5.15 (1H, d, J=13.7 Hz), 5.39 (1H, d, J=13.7 Hz), 7.54 (2H, d, J=8.6 Hz), 7.98 (1H, s), 8.05 (2H, d, J=8.6 Hz), 8.37 (1H, s).

b) Sodium (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-isobutyrylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

The title compound (133 mg) was obtained from 440 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-isobutyrylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate in the same manner as in Example 1-b), except that the purification was carried out by column chromatography on Diaion HP-20 (10% aqueous methanol) and Cosmosil 40C18-PREP (10% aqueous acetonitrile).

NMR (D 2 O) δ (HOD=4.80 ppm): 1.18 (9H, m), 1.32 (3H, d, J=6.5 Hz), 3.44 (1H, m), 3.49 (1H, dd, J=6.3 Hz, J 2 =2.7 Hz), 3.57 (1H, m), 4.27 (1H, m) (1H, dd, J 1 =9.2 Hz, J 2 =2.7 Hz), 7.94 (1H, s), 8.07 (1H, s)

›Example 13

Pivaloyloxymethyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-isobutyrylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 2, 48 mg of the title compound was obtained from 52 mg of sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-isobutyrylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2 -em-3-carboxylate.

NMR (CDCl 3 ) δ: 1.17 (9H, s), 1.26 (9H, m), 1.35 (3H, d, J=6.3 Hz), 3.35 (1H, dd, 6.6 Hz, J 2 =2.8 Hz), 3.49 (1H, m), 3.70 (1H, m), 4.28 (1H, m), 4.39 (1H, dd, J 1 =9.8 Hz, J 2 =2.8 Hz), 5.85 (1H, d, J=5.6 Hz), 5.97 (1H, d, J=5.6 Hz), 8.05 (1H, s), 8.49 (1H, s).

›Example 14

Sodium (5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-propionylimidazo[5,1-b]thiazol-3-yl)-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-propionylimidazo[5,1-b]thiazol-3-yl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 51.8 mg of 4-nitrobenzyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-propionylimidazo[5,1-b]thiazol-3-yl)-1-carbapen-2-em-3-carboxylate was obtained from 168 mg of 4-nitrobenzyl (3R,5R,6S)-6-((1R)-1-hydroxyethyl)-2-oxo-1-carbapenam-3-carboxylate and 272 mg of 7-propionyl-3-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 1.24 (3H, t, J=7.4 Hz), 1.41 (3H, d, J=6.3 Hz), 3.03 (2H, q, J=7.4 Hz), 3.39 (3H, m), 4.33 (1H, m), 4.47 (1H, m), 5.22 (1H, d, J=13.6 Hz), 5.38 (1H, d, J=13.6 Hz), 7.22(1H, s), 7.49 (2H, d, J=8.8 Hz), 7.64 (1H, s), 8.18 (2H, d, J=8.8 Hz)

b) Sodium (5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-propionylimidazo[5,1-b]thiazol-3-yl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-b), the title compound (17.4 mg) was obtained from 51.8 mg of 4-nitrobenzyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-propionylimidazo-[5,1-b]thiazol-3-yl)-1-carbapen-2-em-3-carboxylate.

NMR (D 2 O) δ (HOD=4.80 ppm): 1.19 (3H, t, J=7.4 Hz), 1.33 (3H, d, J=6.2 Hz), 2.97 (2H, q, J=7.4 Hz), 3.25 (1H, dd, J 1 =17.4 Hz, J 2 =10.0 Hz), 3.50 (1H, dd, J 1 =17.4 Hz, J 2 =8.7 Hz), 3.62 (1H, dd, J 1 =5.9 Hz, J 2 =2.8 Hz), 4.30 (1H, m, 4.42 (1H, m), 7.30 (1H, s), 7.92 (1H, s).

›Example 15

Sodium (5R,6S)-2-(7-acetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (5R,6S)-2-(7-Acetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 0.79 g of 4-nitrobenzyl (5R,6S)-2-(7-acetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate was obtained from 2.68 g of 4-nitrobenzyl (3R,5R,6S)-6-((1R)-1-hydroxyethyl)-2-oxo-1-carbapenam-3-carboxylate and 3.86 g of 7-acetyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 1.37 (3H, t, J=6.4 Hz), 2.61 (3H, s), 3.30-3.42 (3H, m), 4.21 (1H, m), 4.35 (1H, m), 5.35 (1H, d, J=13.5 Hz), 5.54 (1H, d, J=14.1 Hz), 7.68 (2H, d, J=14.1 Hz), 7.71 (2H, d, J=8.8 Hz), 8.05 (1H, s), 8.24 (2H, d, J=8.8 Hz), 8.39 (1H, s)MS (TSP): 497 (M + +H).

b) Sodium (5R,6S)-2-(7-Acetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-b), 157 mg of the title compound was obtained from 368 mg of 4-nitrobenzyl (5R,6S)-2-(7-acetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate.

NMR (D 2 O) δ (HOD=4.80 ppm): 1.31 (3H, d, J=6.4 Hz), 2.49 (3H, s), 3.30 (2H, m), 3.51 (1H, dd, J 1 =5.8 Hz, J 2 =3.0 Hz), 4.25 (2H, m), 7.85 (1H, s), 8.11 (1H, s)

›Example 16

Pivaloyloxymethyl (5R,6S)-2-(7-Acetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 2, 18.6 mg of the title compound was obtained from, 22.0 mg of sodium (5R,6S)-2-(7-acetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate and 0.014 ml of pivaloyloxymethyl iodide.

NMR (CDCl 3 ) δ: 1.17 (9H, s), 1.31 (3H, d, J=6.3 Hz), 2.55 (3H, s), 3.22-3.32 (3H, m), 4.19-4.31 (2H, m), 5.83 (1H, d, J=5.6 Hz), 5.95 (1H, d, J=5.6 Hz), 7.95 (1H, s), 8.46 (1H, s) MS (TSP): 476 (M + +H).

›Example 17

Sodium (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-isobutyrlimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (5R,6S)-6-((1R)-Hydroxyethyl)-2-(7-isobutyrylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 360 mg of 4-nitrobenzyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-isobutyrylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate was obtained from 350 mg of 4-nitrobenzyl (3R,5R,6S)-6-((1R)-1-hydroxyethyl)-2-oxo-1-carbapenam-3-carboxylate and 450 mg of 7-isobutyryl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 1.21 (6H, d, J=6.9 Hz), 1.36 (3H, d, J=6.2 Hz), 3.35 (3H, m), 3.64 (1H, m), 4.32 (2H, m), 5.23 (1H, d, J=13.8 Hz), 5.45 (1H, d, J=13.8 Hz), 7.60 (2H, d, J=8.8 Hz), 7.98 (1H, s), 8.11 (2H, d, J=8.8 Hz), 8.25 (1H, s).

b) Sodium (5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-isobutyrylimidazo[5,1-b]thiazol2yl)-1-carbapen-2-em-3-carboxylate

The title compound (178 mg) was obtained from 350 mg of 4-nitrobenzyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-isobutyrylimidazo[5,1-b]thiazol 2-yl)-1-carbapen-2-em-3-carboxylate in the same manner as in Example 1-b), except that the purification was carried out by column chromatography on Diaion HP-20 (10% aqueous methanol) and Cosmosil 40C18-PREP (10% aqueous acetonitrile).

NMR (D 2 O) δ (HOD=4.80 ppm): 1.16 (6H, m), 1.31 (3H, d, J=6.5 Hz), 3.24 (2H, m), 3.42 (2H, m), 4.25 (2H, m), 7.75 (1H, s), 8.01 (1H, s).

›Example 18

Pivaloyloxymethyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-isobutyrylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 2, the title compound (60.8 mg) was obtained from 62 mg of, sodium (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-isobutyrylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate.

NMR (CDCl 3 ) δ: 1.22(9H, s), 1.26 (6H, d, J=6.9 Hz), 1.37 (3H, d, J=6.3 Hz), 3.34 (3H, m), 3.70 (1H, m), 4.31 (2H, m) 5.89 (1H, d, J=5.6Hz), 6.01 (1H, d, J=5.6 Hz), 8.04 (1H, s), 8.54 (1H, s).

›Example 19

Sodium (1S,5R,6S)-2-(7-Acetyl-5-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (1S,5R,6S)-2-(7-Acetyl-5-methylimidazo[5,1-b]thiazol-2-yl)-6-1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 301 mg of 4-nitrobenzyl (1S,5R,6S)-2-(7-acetyl-5-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate was obtained from 455 mg of 4-nitrobenzyl (1R,3R,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-oxo-1-carbapenam-3-carboxylate and 707 mg of 7-acetyl-5-methyl-2 -(tri-n-butylstannyl)imidazo[5,1-b ]thiazole.

NMR (CDCl 3 ) δ: 1.30 (3H, d, J=7.4 Hz), 1.40 (3H, d, J=6.2 Hz), 2.58 (3H, s), 2.66 (3H, s), 3.38 (1H, dd, J 1 =6.5 Hz, J 2 =2.9 Hz), 3.51 (1H, m), 4.32 (1H, m), 4.40 (1H, dd, J 1 =9.5 Hz, J 2 =2.9 Hz), 5.28 (1H, d, J=13.5 Hz), 5.54 (1H, d, J=13.5 Hz), 7.68 (2H, d, J 1 =8.8 Hz), 8.24 (2H, d, J=8.8 Hz), 8.38 (1H, s).

b) Sodium (1S,5R,6S)-2-(7-Acetyl-5-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-b), the title compound (109 mg) was obtained from 155 mg of 4-nitrobenzyl (1S,5R,6S)-2-(7-acetyl-5-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate.

NMR (D 2 O) δ (HOD=4.80 ppm): 1.17 (3H, d, J=7.1 Hz), 1.33 (3H, d, J=6.3 Hz), 2.38 (3H, s), 2.46 (3H, s), 3.46 (1H, m), 3.54 (1H, m), 4.29 (2H, m), 7.69 (1H, s).

›Example 20

Pivaloyloxymethyl (1S,5R,6S)-2-(7-Acetyl-5-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 2, the title compound (37.2 mg) was obtained from 49.1 mg of sodium (1S,5R,6S)-2-(7-acetyl-5-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate.

NMR (CDCl 3 ) δ: 1.20 (9H, s), 1.28 (3H, d, J=7.1 Hz), 1.37 (3H, d, J=6.3 Hz), 2.58 (3H, s), 2.70 (3H, s), 3.35 (1H, dd, J 1 =6.6 Hz, J 2 =2.8 Hz), 3.49 (1H, m), 4.29 (1H, m), 4.38 (1H, dd, J 1 =9.8 Hz, J 2 =2.8 Hz), 5.86 (1H, d, J=5.6 Hz), 6.00 (1H, d, J=5.6 Hz), 8.35 (1H, s).

›Example 21

Sodium (1S,5R,6S)-2-(7-Acetyl-3-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl-1-methyl-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (1S,5R,6S)-2-(7-Acetyl-3-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 237 mg of 4-nitrobenzyl (1S,5R,6S)-2-(7-acetyl-3-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate was obtained from 343 mg of 4-nitrobenzyl (1R,3R,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-oxo-1-carbapenam-3-carboxylate and 533 mg of 7-acetyl-3-methyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 1.19 (3H, d, J=7.2 Hz), 1.39 (3H, d, J=6.3 Hz), 2.28 (3H, s), 2.62 (3H, s), 3.44 (2H, m), 4.33 (1H, m), 4.48 (1H, dd, J 1 =10.2 Hz, J 2 =3.2 Hz), 5.20 (1H, d, J=13.5 Hz), 5.40 (1H, d, J=13.5 Hz), 7.53 (2H, d, J=8.9 Hz), 7.82 (1H, s), 8.16 (2H, d, J=8.9 Hz).

b) Sodium (1S,5R 6S)-2-(7-Acetyl-3-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-b), 130 mg of the title compound was obtained from 237 mg of 4-nitrobenzyl (1S,5R,6S)-2-(7-acetyl-3-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate.

NMR (D 2 O) δ (HOD=4.80 ppm): 1.16 (3H, d, J=7.1 Hz), 1.30 (3H, d, J=6.3 Hz), 2.37 (3H, s), 2.53 (3H, s), 3.37 (1H, m), 3.56 (1H, dd, J 1 =5.8 Hz, J 2 =2.9 Hz), 4.28 (1H, m), 4 .37 (1H, dd, J=9.4 Hz, J 2 =2.9 Hz), 8.20 (1H, s).

›Example 22

Pivaloyloxymethyl (1S,5R,6S)-2-(7-Acetyl-3-methylimidazo[5,1-b]thiazol-2-yl)-6-4(1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 2, the title compound (41.2 mg) was obtained from 48.4 mg of sodium (1S,5R,6S)-2-(7-acetyl-3-methylimidazo[5,1-b]thiazol-2-yl)6-(1R)-1-hydroxyethyl)-1-methyl-carbapen-2-em-3-carboxylate.

NMR (CDCl 3 ) δ: 1.08 (9H, s), 1.18 (3H, d, J=7.4 Hz), 1.37 (3H, d, J=6.3 Hz), 2.39 (3H, s), 2.61 (3H, s), 3.42 (2H, m), 4.30 (1H, m), 4.46 (1H, dd, J=10.1 Hz, J 2 =3.0 Hz), 5.73 (1H, d, J=5.5 Hz), 5.88 (1H, d, J=5.5 Hz), 7.93 (1H, s).

›Example 23

Sodium (5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

In substantially the same manner as in Example 1-a), 453 mg of 4-nitrobenzyl (5R,6S)-6-((3R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate was obtained from 209 mg of 4-nitrobenzyl (3R,5R,6S)-6-((1R)-1-hydroxyethyl)-2-oxo-1-carbapenam-3-carboxylate and 251 mg of 7-methanesulfonyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 1.36 (3H, d, J=6.3 Hz), 3.22 (3H, s), 3.32 (2H, dd, J=7.0 Hz, J 2 =3.1 Hz), 3.36-3.40 (1H, m), 4.20-4.28 (1H, m), 4.30-4.38 (1H, m), 5.34 (1H, d, J=13.5 Hz), 5.52 (1H, d, J=13.5 Hz), 7.70 (2H, d, J=8.9 Hz), 8.13 (1H, s), 8.26 (2H, d, J=8.9 Hz), 8.30 (1H, s).

b) Sodium (5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

The title compound (69.7 mg) was obtained from 282 mg of 4-nitrobenzyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate in substantially the same manner as in Example 1-b), except that the purification was carried out using Cosmosil 40C18-PREP (5% aqueous methanol).

NMR (D 2 O) δ (HOD=4.80 ppm): 1.30 (3H, d, J=6.3 Hz), 3.29 (3H, s), 3.29-3.36 (2H, m), 3.50-3.55 (1H, m), 4.25-4.35 (2H, m) 7.90 (1H, s) 8.25 (1H, s)

›Example 24

Sodium (5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-3-yl)-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-3-yl)-1-carbapen-2-em-3-carboxylate

In substantially the same manner as in Example 1-a), 84 mg of 4-nitrobenzyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-3-yl)-1-carbapen-2-em-3-carboxylate was obtained from 87 mg of 4-nitrobenzyl (3R,5R,6S)-6-((1R)-1-hydroxyethyl)-2-oxo-1-carbapenam-3-carboxylate and 110 mg of 7-methanesulfonyl-3-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 1.40 (3H, d, J=6.3 Hz), 3.20 (3H, s), 3.35-3.45 (3H, m), 4.25-4.33 (1H, m), 4.45-4.52 (1H, m), 5.22 (1H, d, J=13.5 Hz), 5.38 (1H, d, J=13.5 Hz), 7.20 (1H,s), 7.54 (2H, d, J=8.8 Hz), 7.80 (1H, s), 8.20 (2H, d, J=8.8 Hz).

b) Sodium (5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-3-yl)-1-carbapen-2-em-3-carboxylate

The title compound (30.1 mg) was obtained in substantially the same manner as in Example 1-b) from 84 mg of 4-nitrobenzyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-3-yl)-1-carbapen-2-em-3-carboxylate, except that the purification was carried out using Cosmosil 40C18-PREP (5% aqueous methanol).

NMR (D 2 O) δ (HOD=4.80 ppm): 1.30 (3H, d, J=6.3 Hz), 3.22 (1H, dd, J 1 =17.3 Hz, J 2 =9.7 Hz), 3.30 (3H, s), 3.48 (1H, dd J,=17.3 Hz, J 2 =8.2 Hz), 3.59-3.62 (1H, m), 4.23-4.30 (1H, m), 4.35-4.43 (1H, m), 7.25 (1H, s), 8.05 (1H, s).

›Example 25

Sodium (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-3-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-3-yl)-1-carbapen-2-em-3-carboxylate

In substantially the same manner as in Example 1-a), 817 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-3-yl)-1-carbapen-2-em-3-carboxylate was obtained from 797 mg of 4-nitrobenzyl, (1R,6R,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-oxo-1-carbapenam-3-carboxylate and 919 mg of 7-methylthio-3-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (DMSO-d 6 ) δ: 1.06 (3H, d, J=7.2 Hz), 1.17 (3H, d, J=6.3 Hz), 3.32 (3H, s), 3.53-3.57 (1H, m), 3.63-3.70 (1H, m), 4.00-4.08 (1H, m), 4.41 (1H, dd, J 1 =10.3 Hz, J 2 =3.1 Hz), 5.20 (1H, d, J=13.5 Hz), 5.30 (1H, d, J=13.5 Hz), 7.40 (1H, s), 7.45 (2H, d, J=8.3 Hz), 8.15 (2H, d, J=8.3 Hz), 8.19 (1H, s).

b) 4-Nitrobenzyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-3-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

OXONE (manufactured by Du Pont (E.I.) de Nemours & Co.) (123 mg), was added under ice cooling to a solution of 51.4 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate in a mixture of 0.5 ml of THF with 0.5 ml of water, followed by stirring at the same temperature for 40 min. Thereafter, a saturated aqueous sodium hydrogencarbonate solution was added thereto, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate. The solvent was removed by distillation. The residue was purified by column chromatography on silica gel (dichloromethane:methanol=20:1) to give 23.5 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-3-yl)-1-methyl-1-carbapen-2-em-3-carboxylate.

NMR (CDCl 3 ) δ: 1.20 (3H, d, J=7.3 Hz), 1.39 (3H, d, J=6.3 Hz), 3.20 (3H, s), 3.50 (1H, dd, J 1 =6.0 Hz, J 2 =3.2 Hz), 3.58-3.68 (1H, m), 4.30-4.40 (1H, m), 4.56 (1H, dd, J 1 =10.7 Hz, J 2 =3.2 Hz), 5.18 (1H, d, J=13.5 Hz), 5.37 (1H, d, J=13.5 Hz), 7.13 (1H, s), 7.49 (2H, d, J=8.6 Hz), 7.82 (1H, s), 8.20 (2H, d, J=8.6 Hz).

c) Sodium (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-3-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

The title compound (29.8 mg) was obtained from 62.4 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-3-yl)-1-methyl-1-carbapen-2-em-3-carboxylate in substantially the same manner as in Example 1-b), except that the purification was carried out using Cosmosil 40C18-PREP (5% aqueous methanol).

NMR (D 2 O) δ (HOD=4.80 ppm): 1.15 (3H, d, J=7.0 Hz), 1.31 (3H, d, J=6.3 Hz), 3.31 (3H, s), 3.51-3.65 (2H, m), 14.251-4.35 (1H, m), 4.43 (1H, d, J=10.4 Hz), 7.30 (1H, s), 8.16 (1H, s).

›Example 26

Sodium (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfinylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

a) 4-Nitrobenzyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-1-carboxylate

In substantially the same manner as in Example 1-a), 453 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]-thiazol-2-yl)-1-carbapen-2-em-3-carboxylate was obtained from 399 mg of 4-nitrobenzyl (1R,3R,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-oxo-1-carbapenam-3-carboxylate and 442 mg of 7-methylthio-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 1.30 (3H, d, J=7.4 Hz), 1.40 (3H, d, J=6.3 Hz), 2.42 (3H, s), 3.36 (1H, dd, J=6.3 Hz, J=2.5 Hz), 3.40-3.50 (1H, m), 4.29-4.35 (1H, m), 4.38 (1H, dd, J=9.4 Hz, J 2 =2.8 Hz), 5.27 (1H, d, J=13.5 Hz), 5.52 (1H, d, J=13.5 Hz), 7.68 (2H, d, J=8.5 Hz), 8.07 (1H, s), 8.23 (2H, d, J=8.5 Hz), 8.44 (1H, s).

b) 4-Nitrobenzyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfinylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example 25-b), 61 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfinylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers) was obtained using 190 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo-[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate and 227 mg of OXONE (manufactured by Du Pont (E.I.) de Nemours & Co.).

NMR (CDCl 3 ) δ: 1.28, 1.29; (3H, d, J=7.4 Hz), 1.39 (3H, d, J=6.3 Hz), 3.35-3.39 (1H, m), 3.40-3.50 (1H, m), 4.25-4.35 (1H, m), 4.38-4.40 (1H, m), 5.27 (1H, d, J=13.5 Hz), 5.52 (1H, d, J=13.5 Hz), 7.68 (2H, d, J=8.5 Hz), 8.07 (1H, s), 8.23 (2H, d, J=8.5 Hz), 8.44 (1H, s).

c) Sodium (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfinylimidazo[5,1-b]thiazol2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers))

The title compound (23.8 mg) was obtained from 61 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-3-yl)-1-methyl-1-carbapen-2-em-3-carboxylate in substantially the same manner as in Example 1-b), except that the purification was carried out using Cosmosil40C18-PREP (5% aqueous methanol).

NMR (D 2 O) δ (HOD=4.80 ppm): 1.21 (3H, d, J=7.2 Hz), 1.31 (3H, d, J=6.3 Hz), 3.06 (3H, d), 3.45-3.60 (2H, m), 7.94, 7.96 (1H, s), 8.21, 8.22 (1H, s).

›Example 27

Sodium (5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-propionylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-propionylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 362 mg of 4-nitrobenzyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-propionylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate was obtained from 522 mg of 4-nitrobenzyl (3R,5R,6S)-6-((1R)-1-hydroxyethyl)-2-oxo-1-carbapenam-3-carboxylate and 844 mg of 7-propionyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (DMSO-d 6 ) δ: 1.10 (3H, t, J=7.5 Hz), 1.17 (3H, d, J=6.2 Hz), 2.91 (2H, q, J=7.5 Hz), 3.49 (3H, m), 4.01 (1H, m), 4.26 (1H, m), 5.43 (1H, d, J=13.9 Hz), 5.56 (1H, d, J=13.9 Hz), 7.77 (2H, d, J=8.8 Hz), 8.24 (2H, d, J=8.8 Hz), 8.32 (1H, s), 8.47 (1H, s).

b) Sodium (5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-propionylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-b), 91.2 mg of the title compound was obtained from 162 mg of 4-nitrobenzyl (5R,6S)-76-((1R)-1-hydroxyethyl)-2-(7-propionylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate.

NMR (D 2 O) δ (HOD=4.80 ppm): 1.11 (3H, t, J=6.9 Hz), 1.32 (3H, d, J=6.3 Hz), 2.77 (2H, q, J=6.9 Hz), 3.20 (2H, m) 3.48 (1H, dd, J,=5.7 Hz, J 1 =2.5 Hz), 4.25 (2H, m), 7.65 (1H, s), 7.93 (1H, s).

›Example 28

Pivaloyloxymethyl (5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-propionylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate.

In the same manner as in Example 2, 28.6 mg of the title compound was obtained from 50.2 mg of sodium (5R,6S)-6-((1R)-1-hydroxyethyl-2-(7-propionylimidazo[5,1-b]-thiazol-2-yl)-1-carbapen-2-em-3-carboxylate.

NMR (CDCl 3 ) δ: 1.22 (9H, s), 1.26 (3H, t, J=7.4 Hz), 1.38 (3H, d, J=6.3 Hz), 3.06 (2H, q, 37.4 Hz), 3.32 (3H, m), 4.31 (2H, m), 5.90 (1H, d, J=5.6 Hz), 6.02 (1H, d, J=5.6 Hz,), 8.02 (1H, s), 8.55 (1H, s).

›Example 29

Pivaloyloxymethyl (5R,6S)-2-(7-Acetylimidazo[5,1-b]thiazol-3-yl)-6-((1R)-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (5R,6S)-2-7-Acetylimidazo[5,1-b]thiazol-3-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 312 mg of 4-nitrobenzyl (5R,6S)-2-(7-acetylimidazo[5,1-b]thiazol-3-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate was obtained from 396 mg of 4-nitrobenzyl (3R,5R,6S)-6-((1R)-1-hydroxyethyl)-2-oxo-1-carbapenam-3-carboxylate and 621 mg of 7-acetyl-3-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 1.40 (3H, d, J=6.3 Hz), 2.58 (3H, s), 3.42 (3H, m), 4.33 (1H, m), 4.48 (1H, m), 5.20 (1H, d, J=13.5 Hz), 5.37 (1H, d, J=13.5 Hz), 7.22 (1H, s), 7.47 (2H, d, J=8.6 Hz), 7.67 (1H, s), 8.17 (2H, d, J=8.6 Hz).

b) Sodium (5R,6S)-2-(7-Acetylimidazo[5,1-b]thiazol-3-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-b), 109 mg of sodium (5R,6S)-2-(7-acetylimidazo[5,1-b]thiazol-3-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate was obtained from 216 mg of 4-nitrobenzyl (5R,6S)-2-(7-acetylimidazo[5,1-b]thiazol-3-yl)-6-1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate.

NMR (D 2 O) δ (HOD=4.80 ppm): 1.32 (3H, t, J=6.3 Hz), 2.50 (3H, s), 3.23 (1H, dd, J 1 =17.1 Hz, J 2 =9.9 Hz), 3.48 (1H, dd, J 1 =17.1 Hz, J 2 =8.5 Hz), 3.60 (1H, dd, J 1 =5.8 Hz, J 2 =2.7 Hz), 4.28 (1H, m), 4.41 (1H, m), 7.27 (1H, s), 7.83; (1H, s);

c) Pivaloyloxymethyl (5R,6S)-2-(7-Acetylimidazo[5,1-b]thiazol-3-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 2, 61.3 mg of the title compound was obtained from 69.4 mg of sodium ((5R,6S)-2-(7-acetylimidazo[5,1-b]thiazol-3-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate.

NMR (CDCl 3 ) δ: 1.19 (9H, s), 1.39 (3H, d, J=6.2 Hz), 2.61 (3H, s), 3.37 (3H, m), 4.30 (1H, m), 4.44 (1H, m), 5.77 (1H, d, J=5.6 Hz), 5.89 (1H, d, J=5.6 Hz), 7.26 (1H, s), 7.73 (1H, s).

›Example 30

Sodium (1S,5R,6S)-2-(7-Ethaneslfonylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (1S,5R,6S)-2-(7-Ethanesulfonylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 765 mg of 4-nitrobenzyl (1S,5R,6S)-2-(7-ethanesulfonylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate was obtained from 262 mg of 4-nitrobenzyl (1R,3R,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-oxo-1-carbapenam-3-carboxylate and 413 mg of 7-ethanesulfonyl-2-(tri-n-butylstannyl)imidazo[5,1-b]-thiazole.

NMR (CDCl 3 ) δ: 1.31 (3H, t, J=17.4 Hz), 1.34 (3H, d, J=7.4 Hz), 1.39 (3H, d, J=6.3 Hz), 3.31 (2H, q, J=7.4 Hz), 3.38 (1H, dd, J 1 =6.6 Hz, J 2 =2.7 Hz), 3.50 (1H, m), 4.31 (1H, m), 4.40 (1H, dd, J 1 =9.6 Hz, J 2 =2.7 Hz), 5.27 (1H, d, J=13.7 Hz), 5.51 (1H, d, J 1 =13.7 Hz), 7.67 (2H, d, J=8.8 Hz), 8.08 (1H, s), 8.22 (2H, d, J=8.8 Hz), 8.42 (1H, s).

b) Sodium (1S,5R,6S)-2-(7-Ethanesulfonylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-b), 139 mg of the title compound was obtained from 232 mg of 4-nitrobenzyl (1S,5R,6S)-2-(7-ethanesulfonylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate.

NMR (D 2 O) δ (HOD=4.80 ppm): 1.22 (3H, t, J=7.4 Hz), 1.25 (3H, d, J=7.4 Hz), 1.31 (3H, d, J=6.3 Hz), 3.37 (2H, q, J=7.4 Hz), 3.48 (1H, m), 3.56 (1H, m), 4.23-4.30 (2H, m) 7.97 (1H, s), 8.19 (1H, s).

›Example 31

Sodium (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-1-methyl-2-(7-N-methylsulfamoylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-1-methyl-2-(7-N-methylsulfamoylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

In substantially the same manner as in Example 1-a), 307 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-N-methylsulfamoylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate was obtained from 362 mg of 4-nitrobenzyl (1R,3R,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-oxo-1-carbapenam-3-carboxylate and 327 mg of 7-N-methylsulfamoyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (DMSO-d 6 ) δ: 1.18 (3H, d, J=6.1 Hz), 1.22 (3H, d, J=7.2 Hz), 2.43 (3H, d, J=5.1 Hz), 3.42 (1H, dd, J 1 =5.7 Hz, J 2 =2.8 Hz), 3.70-3.76 (1H, m), 4.00-4.06 (1H, m), 4.43 (1H, dd, J 1 =9.9 Hz, J 2 =2.8 Hz), 5.16 (1H, d, J=5.0 Hz), 5.39 (1H, d, J=13.6 Hz), 5.53 (1H, d, J=13.6 Hz), 7.50 (1H, q, J=5.1 Hz), 7.73 (2H, d, J=8.5 Hz), 8.22 (2H, d, J=8.5 Hz), 8.38 (1H, s), 8.53 (1H, s).

b) Sodium (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-1-methyl-2-(7-methylsulfamoylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

In substantially the same manner as in Example 1-b), the title compound (182 mg) was obtained from 307 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-N-methylsulfamoylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate, except that the purification was carried out using Colsmosil 40C18-PREP (5% aqueous methanol).

NMR (D 2 O) δ (HOD=4.80 ppm): 1.26 (3H, d, J=7.4 Hz), 1.32 (3H, d, J=6.3 Hz), 2.60 (3H, s), 3.52-3.56 (1H, m), 3.60-3.70 (1H, m), 4.25-4.35 (2H, m), 8.05 (1H, s), 8.26 (1H, s).

›Example 32

Sodium (5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-N-methylsulfamoylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-N-methylsulfamoylimidazo[5,1-b]thiazol-2yl)-1-carbapen-2-em-3-carboxylate

In substantially the same manner as in Example 1-a), 104 mg of 4-nitrobenzyl, (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-N-methylsulfamoylimidazo[5,1-b](thiazol-2-yl)-1-carbapen-2-em-3-carboxylate was obtained from 139 mg of 4-nitrobenzyl (3R,5R,6S)-6-((1R)-1-hydroxyethyl)-2-oxo-1-carbapenam-3-carboxylate and 164 mg of 7-N-methylsulfamoyl-2-(tri-n-butylstannyl)imidazo[5,1-b]-thiazole.

NMR (DMSO-d 6 ) δ: 1.16 (3H, d, J=6.3 Hz), 2.41 (3H, d, J=4.0 Hz), 3.43-3.55 (3H, m), 3.96-4.05 (1H, m), 4.20-4.30 (1H, m), 5.18 (1H, d, J=13.8 Hz), 5.56 (1H, d, J=13.8 Hz), 7.51 (1H, q, J=4.9 Hz), 7.76 (2H, d, J=8.4 Hz), 8.25 (2H, d, J=8.4 Hz), 8.39 (1H, s), 8.44 (1H, s).

b) Sodium (5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-N-methylsulfamoylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

The title compound (54.3 mg) was obtained from 100 mg of 4-nitrobenzyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-N-methylsulfamoylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate in substantially the same manner as in Example 1-b), except that the purification was carried out using Colsmosil 40C18-PREP (5% aqueous methanol).

NMR (D 2 O) δ (HOD=4.80 ppm): 1.30 (3H, d, J=6.3 Hz), 2.50 (3H, s), 3.30-3.40 (2H, m), 3.51-3.55 (1H, m), 4.23-4.35 (2H, m), 7.90 (1H, s), 8.24 (1H, s).

›Example 33

Sodium (5R,6S)-2-(7-Acetyl-5-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl-3-carboxylate.

a) 4-Nitrobenzyl (5R,6S)-2-(7-Acetyl-5-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 380 mg of 4-nitrobenzyl (5R,6S)-2-(7-acetyl-5-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate was obtained from 480 mg of 4-nitrobenzyl (3R,5R,6S)-6-((1R)-1-hydroxyethyl)-2-oxo-1-carbapenam-3-carboxylate and 776 mg of 7-acetyl-5-methyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 1.40 (3H, d, J=6.3 Hz), 2.58 (3H, s), 2.66 (3H, m), 3.36 (3H, m), 4.35 (2 H, m), 5.32 (1H, d, J=13.3 Hz), 5.56 (1H, d, J=13.3 Hz), 7.70 (2H, d, J=8.9 Hz), 8.25 (2H, d, J=8.9 Hz), 8.30 (1H, s).

b) Sodium (5R,6S)-2-(7-Acetyl 5-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-b), 110 mg of the title compound was obtained from 173 mg of 4-nitrobenzyl (5R,6S)-2-(7-acetyl-5-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate.

NMR (D 2 O) δ (HOD=4.80 ppm): 1.32 (3H, t, J=6.3 Hz), 2.35 (3H, s), 2.36 (3H, s), 3.11 (2H, m), 3.48 (1H, dd, J 1 =5.3 Hz, J 2 =2.6 Hz), 4.23 (2H, m), 7.40 (1H, s).

›Example 34

Sodium (5R,6S)-2-(7-Ethanesulfonylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (5R,6S)-2-(7-Ethanesulfonylimidazo[5,1-b]thiazol-2-yl-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 74.2 mg of 4-nitrobenzyl (5R,6S)-2-(7-ethanesulfonylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate was obtained from 253 mg of 4-nitrobenzyl (3R,5R,6S)-6-((1R)-1-hydroxyethyl)-2-oxo-1-carbapenam-3-carboxylate and 396 mg of 7-ethanesulfonyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 1.20 (3H, t, J=7.0 Hz), 1.39 (3H, d, J=6.2 Hz), 3.26-3.40 (4H, m), 3.48 (2H, q, J=7.0 Hz), 4.32 (1H, m), 5.29 (1H, d, J=13.7 Hz), 5.52 (1H, d, J=13.7 Hz), 7.68 (2H, d, J=8.8 Hz), 7.85 (1H, s), 8.15 (1H, s), 8.21 (2H, d, J=8.9 Hz).

b) Sodium (5R,6S)-2-(7-Ethanesulfonylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-b), 10.5 mg of the title compound was obtained from 74.2 mg of 4-nitrobenzyl (1S,5R,6S)-2-(7-ethanesulfonylimidazo[5,1 b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl 1-carbapen-2-em-3-carboxylate.

NMR (D 2 O) δ (HOD=4.80 ppm): 1.24 (3H, t, J=7.4 Hz), 1.30 (3H, d, J=6.6 Hz), 3.27 (2H, m), 3.39 (2H, q, J=7.4 Hz), 3.50 (1H, m), 4.25 (2H, m), 7.84 (1H, s), 8.20 (1H, s).

›Example 35

Sodium (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-1-methyl-2-(7-p-toluenesulfonylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carbdxylate

a) 4-Nitrobenzyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-1-methyl-2-(7-p-toluenesulfonylimidazo-[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 176 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-p-toluenesulfonylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate was obtained from 350 mg of 4-nitrobenzyl (1R,3R,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-oxo-1-carbapenam-3-carboxylate and 590 mg of 7-p-toluenesulfonyl-2-(tri-n-butylstannyl)imidazo[5,1-b]-thiazole.

NMR (CDCl 3 ) δ: 1.29 (3H, t, J=!7.1 Hz), 1.39 (3H, d, J=6.3 Hz), 2.40 (3H, s), 3.37 (1H, dd, J 1 =6.6 Hz, J 2 =2.8 Hz), 3.52 (1H, m), 4.30 (1H, m), 4.40 (1H, dd, J 1 =9.6 Hz, J 2 =2.8 Hz), 5.26 (1H, d, J=13.7 Hz), 5.50 (1H, d, J=13.7 Hz), 7.29 (2H, d, J=8.4 Hz), 7.29 (2H, d, J=8.4 Hz), 7.66 (2H, d, J=8.9 Hz), 7.91 (2H, d, J=8.4 Hz), 7.99 (1H, s), 8.20 (2H, d, J=8.9 Hz), 8.35 (1H, s); MS (TSP): 623 (M + +H).

b) Sodium (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-1-methyl-2-(7-p-toluenesulfonylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-b), 53.0 mg of the title compound was obtained from 176 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-p-toluenesulfonylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate.

NMR (D 2 O) δ (HOD=4.80 ppm): 1.17 (3H, t, J=7.1 Hz), 1.31 (3H, d, J=6.3 Hz), 2.34 (3H, s), 3.47 (2H, m), 4.25 (2H, m), 7.35 (2H, d, J=8.3 Hz), 7.77 (2H, d, J=8.3 Hz), 7.94 (1H, s), 8.12 (1H, s).

›Example 36

Sodium (5R,6S)-2-(7-Hydroxyacetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

4-Nitrobenzyl (5R,6S)-2-(7-t-Butyldimethylsilyloxyacetylimidazo[5,1-b]thiazol-2yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 255 mg of 4-nitrobenzyl (5R,6S)-2-(7-t-butyldimethylsilyloxyacetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate was obtained from 325 mg of 4-nitrobenzyl (3R,5R,6S)-6-((1R)-1-hydroxyethyl)-2-oxo-1-carbapenam-3-carboxylate and 655 mg of 7-t-butyldimethylsilyloxyacetyl-2-(tri-n-butylstannyl)-imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 0.15 (6H, s), 0.96 (9H, s), 1.41 (3H, d, J=6.3 Hz), 3.35 (3H, m), 4.34 (2H, m), 5.08 (2H, s), 5.31 (1H, d, J=13.4 Hz), 5.53 (1H, d, J=13.4 Hz), 7.69 (2H, d, J=8.9 Hz), 7.97 (1H, s), 8.23 (2H, d, J=8.9 Hz), 8.42 (1H, s).

b) 4-Nitrobenzyl (5R,6S)-2-(7-Hydroxyacetylimidazo[5,1-b]thiazol-2-yl)-6-( (1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

Acetic acid (0.345 ml) and 2.04 ml of a 1 M tetra-n-butylammonium fluoride/THF solution were added to a solution of 255 mg of 4-nitrobenzyl (5R,6S)-2-(7-t-butyldimethylsilyloxyacetylimidazo[5,1 -b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate in 8 ml of THF. The mixture was stirred at room temperature for 3 hr. Brine was added to the reaction solution. The mixture was adjusted to pH 8.1 by the addition of a saturated sodium hydrogencarbonate solution, and extracted twice with ethyl acetate. The organic layers were combined, washed twice with brine, and dried over anhydrous magnesium sulfate. The solvent was removed by distillation under the reduced pressure. Diethyl ether(5 ml) was added to the residue. The insoluble was collected by filtration to give 196 mg of 4-nitrobenzyl (5R,6S)-2-(7-hydroxyacetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate.

NMR (CDCl 3 ) δ: 1.17 (3H, d, J=6.5 Hz), 3.50 (3H, m), 4.01 (1H, m), 4.27 (1H, m), 4.69 (2H, s), 5.44 (1H, d, J=13.8 Hz), 5.58 (1H, d, J=13.8 Hz), 7.77 (2H, d, J=8.9 Hz), 8.25 (2H, d, J=8.9 Hz), 8.34 (1H, s), 8.50 (1H, s).

c) Sodium (5R,6S)-2-(7-Hydroxyacetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-b), 95.9 mg of the title compound was obtained from 196.6 mg of 4-nitrobenzyl (5R,6S)-2-(7-hydroxyacetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate.

NMR (D 2 O) δ (HOD=4.80 ppm): 1.33 (3H, d, J=6.1 Hz), 3.24 (2H, m), 3.50 (1H, m), 4.27 (2H, m), 4.77 (2H, s), 7.75 (1H, s), 8.02 (1H, s).

›Example 37

Sodium (1S,5R,6S)-2-(7-Benzoylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (1S,5R,6S)-2-(7-Benzoylimidazo[5,1-b]thiazol-2-yl)-6 ((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 288 mg of 4-nitrobenzyl (1S,5R,6S)-2-(7-benzoylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate was obtained from 543 mg of 4-nitrobenzyl (1R,3R,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-oxo-1-carbapenam-3-carboxylate and 931 mg of 7-benzoyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (DMSO-d 6 ) δ: 1.19 (3H, d, J=6.2 Hz), 1.25 (3H, d, J=7.1 Hz), 3.45 (1H, dd, J 1 =5.7 Hz, J 2 =2.7 Hz), 3.77 (1H, m), 4.04 (1H, m), 4.37, (1H, dd, J 1 =10.1 Hz, J 2 =2.7 Hz), 5.41 (1H, d, J=14.0 Hz), 5.55 (1H, d, J=14.0 Hz), 7.58 (3H, m), 7.75 (2H, d, J=8.8 Hz), 8.22 (2H, d, J=8.8 Hz), 8.44 (1H, s), 8.49 (2H, m), 8.62 (1H, s).

b) Sodium (1S,5R,6S)-2-(7-Benzoylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

The title compound (120 mg) was obtained from 440 mg of 4-nitrobenzyl (1S,5R,6S)-2-(7-benzoylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate in the same manner as in Example 1-b), except that the purification was carried out by column chromatography on Diaion HP-20 (30% aqueous methanol) and Cosmosil, 40C18-PREP (30% aqueous methanol).

NMR (D 2 O) δ (HOD=4.80 ppm): 1.10 (3H, d, J=7.1 Hz), 1.32 (3H, d, J=6.3 Hz), 3.44 (2H, m), 4.23 (2H, m), 7.42 (2H, m), 7.57 (1H, m), 7.87 (3H, m), 8.01 (1H, s).

›Example 38

Sodium (5R,6S)-2-(7-Hydroxyacetylimidazo[5,1- b]thiazol-3-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (5R,6S)-2-(7-t-Butyldimethylsilyloxyacetylimidazo[5,1-b]thiazol-3-yl)-6-((1R)-1-hydroxyethyl)-1-2-em-3-carboxylate

In the same manner as in Example 1-a), 167 mg of 4-nitrobenzyl (5R,6S)-2-(7-t-butyldimethylsilyloxyacetylimidazo[5,1-b]thiazol-3-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate was obtained from 293 mg of 4-nitrobenzyl (3R,5R,6S)-6-((1R)-1-hydroxyethyl)-2-oxo-1-carbapenam-3-carboxylate and 591 mg of 7-t-butyldimethylsilyloxyacetyl-3-(tri-n-butylstannyl)-imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 0.15 (6H, s), 0.96 (9H, s), 1.40 (3H, d, J=6.3 Hz), 3.41 (3H, m), 4.31 (1H, m), 4.48 (1H, m), 5.05 (2H, s), 5.21 (1H, d, J=13.5 Hz), 5.38 (1H, d, J=13.5 Hz), 7.24 (1H, s), 7.50 (2H, d, J=8.9 Hz), 7.66 (1H, s), 8.18 (2H, d, J=8.9 Hz)

b) 4-Nitrobenzyl (5R,6S)-2-(7-Hydroxyacetylimidazo[5,1-b]thiazol-3-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 36-b), 56.5 mg of 4-nitrobenzyl (5R,6S)2-(7-hydroxyacetylimidazo[5,1-b]thiazol-3-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate was obtained from 167 mg of 4-nitrobenzyl (5R,6S)2-(7-t-butyldimethylsilyloxyacetylimidazo[5,1-b]thiazol-3-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate.

NMR (CDCl 3 ) δ: 1.41 (3H, d, J=6.3 Hz), 3.40 (3H, m), 4.34 (1H, m), 4.48 (1H, m), 4.88 (2H, s), 5.22 (1H, d, J=13.4 Hz), 5.39 (1H, d, J=13.4 Hz), 7.52 (2H, d, J=8.6 Hz), 7.67 (1H, s), 8.20 (3H, m).

c) Sodium (5R,6S)-2-(7-Hydroxyacetylimidazo[5,1-b]thiazol-3-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

The title compound (27.7 mg) was obtained from 56.5 mg of 4-nitrobenzyl (5R,6S)-2-(7-hydroxyacetylimidazo[5,1-b]thiazol-3-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate in the same manner as in Example 1-b), except that the purification was carried out by column chromatography on Diaion HP-20 (10% aqueous methanol) and Cosmosil 40C18-PREP (5% aqueous methanol).

NMR (D 2 O) δ (HOD=4.80 ppm): 1.31 (3H, d, J=6.5 Hz), 3.23 (1H, dd, J 1 =17.5 Hz, J 2 =10.1 Hz), 3.48 (1H, dd, J 1 =17.5 Hz, J 2 =8.8 Hz), 3.60 (1H, dd, J 1 =5.8 Hz, J 2 =2.9 Hz) 4.28 (1H, m), 4.40 (1H, m), 4.89 (2H, s), 7.31 (1H, s), 7.93 (1H, s).

›Example 39

Sodium (5R,6S)-2-(7-Benzmylimidazo[5,1-b]thiazol-2-6-((1R-1-hydroxyethyl)-1-carbapen-2-em-carboxylate

a) 4-Nitrobenzyl (5R,6S)-2-(7-Benzoylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 574 mg of 4-nitrobenzyl (5R,6S)-2-(7-benzoylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate was obtained from 522 mg of 4-nitrobenzyl (3R,5R,6S)-6-((1R)-1-hydroxyethyl)-2-oxo-1-carbapenam-3-carboxylate and 931 mg of 7-benzoyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 1.41 (3H, d, J=6.4 Hz), 3.37 (3H, m), 4.25 (2H, m), 5.33 (1H, d, J=13.5 Hz), 5.56 (1H, d, J=13.5 Hz), 7.54 (3H, m), 7.71 (2H, d, J=8.8 Hz), 8.08 (1H, s), 8.25 (2H, d, J=8.8 Hz), 8.52 (1H, s), 8.54 (2H, m).

b) Sodium (5R,6S)-2-(7-Benzoylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroyethyl)-1-carbapen-2-em-3-carboxylate

The title compound (178 mg) was obtained from 504 mg of 4-nitrobenzyl (5R,6S)-2-(7-benzoylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate in the same manner as in Example 1-b), except that the purification was carried out by column chromatography on Diaion HP-20 (30% aqueous methanol) and Cosmosil 40C18-PREP (20% aqueous methanol).

NMR (D 2 O) δ (HOD=4.80 ppm): 1.26 (3H, d, J=6.3 Hz), 2.90 (2H, m), 3.25 (1H, dd, J 1 =5.8 Hz, J 2 =2.8 Hz), 4.00 (1H, m), 4.17 (1H, m), 7.38 (2H, m), 7.53 (2H, m), 7.83 (3H, m).

›Example 40

Sodium (1S,5R,6S)-2-[7-[N-(4-Aminobenzyl)sulfamoyl]imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-1-methyl-2-[7-[N-(4-nitrobenzyl)sulfamoyl]imidazo[5,1-b]thiazol-2-yl]-carbapen-2-em-3-carboxylate

In substantially the same manner as in Example 1-a), 337 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-[7-[N-(4-nitrobenzyl)-sulfamoyl]imidazo[5,1-b]thiazol-2-yl -1-carbapen-2-em-3-carboxylate was obtained from 507 mg of 4-nitrobenzyl (1R,3R,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-oxo-1-carbapenam-3-carboxylate and 392 mg of 7-N-(4-nitrobenzyl)sulfamoyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (DMSO-d 6 ) δ: 1.15-1.22 (6H, m), 3.41-3.44 (1H, m), 3.65-3.74 (1H, m), 4.00-4.05 (1H, m), 4.17 (2H, d, J=6.3 Hz), 4.30-4.36 (1H, m), 5.17 (11H, d, J=5.1 HZ), 5.40 (1H, J=13.5 Hz), 5.53 (1H, d, J=13.5 Hz), 7.45 (2H, d, J=8.6 Hz), 7.74 (2H, d, J=8.61 Hz), 8.03 (2H, d, J=8.8 Hz), 8.22 (2H, d, J=8.8 Hz), 8.29 (1H, s), 8.43 (1H, s), 8.50 (1H, t, J=6.3 Hz).

b) Sodium (1S,5R,6S)-2-[7-[N-(4-Aminobenzyl)sulfamoyl]imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In substantially the same manner as in Example 1-b), 165 mg of the title compound was obtained from 337 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-[7-[N-(4-nitrobenzyl)sulfamoyl]imidazo[5,1-b]-thiazol-2-yl]-1-carbapen-2-em-3-carboxylate, except that the purification was carried out using Cosmosil 40C18-PREP (5% aqueous methanol).

NMR (D 2 O) δ (HOD=4.80 ppm): 1.26(3H, d, J=7.3 Hz), 1.32 (31H, d, J=6.4 HZ), 3.52-3.64 (11, m), 4.10 (2H, s), 4.25-4.35 (2H, m), 6.46 (2H, d, J=8.5 Hz), 6.86 (2H, d, J=8.6 HZ), 7.90 (1H, s), 7.96 (1H, s).

›Example 41

Sodium (1S,5R,6S)-2-(7-Fluoroimidazo[5,1-b]thiazol-2-yl)-6((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (1S,5R,6s)-2-7-Fluoroimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 40 mg of 4-nitrobenzyl (1S,5R,6S)-2-(7-fluoroimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate was obtained from 320 mg of 4-nitrobenzyl (1R,3R,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-oxo-1-carbapenam-3-carboxylate and 400 mg of 7-fluoro-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 1.31 (3H, d, J=7.4 Hz), 1.39 (3H, d, J=6.3 Hz), 3.39 (1H, dd, J 1 =6.4 Hz, J 2 =2.8 Hz), 3.46 (1H, m), 4.27 (1H, m), 4.40 (1H, dd, J 1 =9.7 Hz, J 2 =2.8 Hz), 5.27 (1H, d, J=13.6 Hz), 5.51 (1H, d, J=13.6 Hz), 7.62 (1H, s), 7.68 (2H, d, J=8.9 Hz), 8.21 (1H, s), 8.26 (2H, d, J=8.9 Hz).

b) Sodium (1S,5R,6S)-2-(7-Fluoroimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-b), 3.8 mg of the title compound was obtained from 40 mg of 4-nitrobenzyl (1S,5R,6S)-2-(7-fluoroimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate.

NMR (D 2 O) δ (HOD=4.80 ppm): 1.24 (3 H, d, J=7.4 Hz), 1.32 (3H, d, J=6.3 Hz), 3.51 (1H, dd, J 1 =6.3 Hz, J 2 =2.7 Hz), 3.53 (1H, m), 4.27 (1H, m), 4.30 (1H, dd, J 1 =9.2 Hz, J 2 =2.71 Hz), 7.72 (1H, s), 7.79 (1H, d, J=1.9 Hz).

›Example 42

Sodium (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-[7-[N-(2-hydroxyethyl)-N-methylsulfamoyl]imidazo[5,1-b]-thiazol-2-yl]-1-methyl-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (1S,5R,6S)-2-[7-[N-(2-t-Butyldimethylsilyloxyethyl)-N-methylsulfamoyl]imidazo-[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In substantially the same manner as in Example 1-a), 273, mg of 4-nitrobenzyl (1S,5R,6S)-2-[7-[N-(2-t-butyldimethylsilyloxyethyl)-N-methylsulfamoyl]imidazo-[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate was obtained from 217 mg of 4-nitrobenzyl (1R,3R,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-oxo-1-carbapenam-3-carboxylate and 362 mg of 7-[N-(1-t-butyldimethylsilyloxyethyl)-N-methylsulfamoyl]-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 0.07 (6H, s), 0.89 (9H, s), 1.32 (3H, d, J=7.2 Hz), 1.41 (3H, d, J=16.2 Hz), 2.99 (3H, s), 3.33 (2H, t, J=6.1 Hz), 3.38 (1H, dd, J 1 =6.4 Hz, J 2 =3.3 Hz), 3.45-3.53 (1H, m), 3.84 (1H, t, J=6.1 Hz), 4.30-4.37 (1H, m), 4.40 (1H, dd, J 1 =9.6 Hz, J 2 =3.3 Hz), 5.30 (1H, d, J=8.5 Hz), 5.54 (1H, d, J=8.5 Hz), 7.69 (2H, d, J=8.5 Hz), 8.05 (1H, s), 8.26 (2H, d, J=8.5 Hz), 8.46 (1H, s).

b) 4-Nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-[7-[N-(2-hydroxyethyl)-N-methyl-sulfamoyl]imidazo[5,1-b]thiazol-2-yl]-1-methyl-1-carbapen-2-em-3-carboxylate

Acetic acid (0.36 ml) and 2.0 ml of a 1 M-tetra-n-butylammonium fluoride/THF solution were added under ice cooling to a solution of 273 mg, of 4-nitrobenzyl (1S,5R,6S)-2-[7-[N-(2-t-butyldimethylsilyloxyethyl)-N-methylsulfamoyl]imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate in 8 ml of THF. The mixture was stirred at room temperature for 6 hr. The reaction mixture was added to a dilute aqueous sodium hydrogencarbonate solution, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate. The solvent was removed by distillation. The residue was purified by column chromatography on silica gel (dichloromethane:methanol=10:1) to give 175 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-[7-[N-(2-hydroxyethyl)-N-methyl-sulfamoyl]imidazo[5,1-b]thiazol-2-yl]-1-methyl-1-carbapen-2-em-3-carboxylate.

NMR (CDCl 3 ) δ: 1.30 (3H, d, J=7.2 Hz), 1.39 (3H, d, J=6.3 Hz), 2.87 (3H, s), 3.38 (1H, dd, J 1 =6.6 Hz, J 2 =2.7 Hz), 3.48-3.53 (1H, m), 3.54 (2H, t, J=4.8 Hz), 3.82 (2H, t, J=4.8 Hz), 4.27-4.37 (1H, m), 4.40 (1H, dd, J 1 =9.7 Hz, J 2 =2.7 Hz), 5.28 (1H, d, J=13.7 Hz), 5.52 (1H, d, J=13.7 Hz), 7.67 (2H, d, J=8.8 Hz), 8.05 (1H, s), 8.23 (2H, d, J=8.8 Hz), 8.42 (1H, s).

c) Sodium (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-[7-[N-(2-hydroxyethyl)-N-methylsulfamoyl]imidazo[5,1-b]-thiazol-2-yl]-1-methyl-1-carbapen-2-em-3-carboxylate

The title compound (90.9 mg) was obtained from 175 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-[7-[N-(2-hydroxyethyl)-N-methylsulfamoyl]imidazo[5,1-b]-thiazol-2-yl]-1-methyl-1-carbapen-2-em-3-carboxylate in substantially the same manner as in Example 1-b), except that the purification was carried out using Cosmosil 40C18-PREP (2.5% aqueous methanol).

NMR (D 2 O) δ (HOD=4.80 ppm): 1.24 (3H, d, J=7.2 Hz), 1.31 (3H, d, J=6.3 Hz), 2.83 (3H, s), 3.27 (2H, t, J=4.9 Hz), 3.51 (1H, m), 3.56-3.67 (1H, m), 3.72 (2H, t, J=4.9 Hz), 4.23-4.35 (2H, m), 8.04 (1H, s), 8.22 (1H, s).

›Example 43

Sodium (1S,5R,6S)-2-(7-Acetylaminoacetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (1S,5R,6S)-2-(7-Acetylaminoacetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 23.8 mg of 4-nitrobenzyl (1S,5R,6S)-2-(7-acetylaminoacetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate was obtained from 123 mg of 4-nitrobenzyl (1R,3R,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-oxo-1-carbapenam-3-carboxylate and 207 mg of 7-acetylaminoacetyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 1.30 (3H, d, J=7.1 Hz), 1.40 (3H, d, J=6.2 Hz), 2.10 (3H, s), 3.39 (1H, dd, J 1 =6.7 Hz, J 2 =2.9 Hz), 3.52 (1H, m), 4.32 (1H, m), 4.42 (1H, dd, J 1 =9.8 Hz, J 2 =2.9 Hz), 4.79 (2H, d, J=4.7 Hz), 5.28 (1H, d, J=13.4 Hz), 5.52 (1H, d, J=13.4 Hz), 6.51 (1H, br), 7.68 (2H, d, J=8.5 Hz), 8.01 (1H, s), 8.24 (2H, d, J=8.5 Hz), 8.46 (1H, s).

b) Sodium (1S,5R,6S)-2-(7Acetylaminoacetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

The title compound (9.0 mg) was obtained from 23.8 mg of 4-nitrobenzyl (1S,5R,6S)-2-(7-acetylaminoacetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate in the same manner as in Example 1-b), except that the purification was carried out by column chromatography on Diaion HP-20 (10% aqueous methanol) and Cosmosil 40C18-PREP (5% aqueous methanol).

NMR (D 2 O) δ (HOD=4.80 ppm): 1.23 (3H, d, J=6.9 Hz), 1.33 (3H, d, J=6.3 Hz), 2.14 (3H, s), 3.52 (2H, m), 4.29 (2H, m), 4.49 (1H, d, J=18.9 Hz), 4.63 (1H, d, J=18.9 Hz) 7.92 (1H, s), 8.07 (1H, s).

›Example 44

Sodium (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonyl-5-methylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-1-methyl-2-(5-methyl-7-methylthioimidazo-[5,1b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 1.41 g of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(5-methyl-7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate was obtained from 1.81 g of 4-nitrobenzyl (1R,3R,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-oxo-1-carbapenam-3-carboxylate and 2.84 g of 5-methyl-7-methylthio-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 1.31 (3H, d, J=7.3 Hz), 1.40 (3H, d, J=6.3 Hz), 2.40 (3H, s), 2.58 (3H, s), 3.36 (1H, dd, J 1 =6.6 Hz, J 2 =3.0 Hz), 3.46 (1H, m), 4.34 (2H, m), 5.27 (1H, d, J=13.7 Hz), 5.54 (1H, d, J=13.7 Hz), 7.68 (2H, d, J=8.9 Hz), 8.16 (1H, s), 8.25 (2H, d, J=8.9 Hz).

b) 4-Nitrobenzyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonyl-5methylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

4-Nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(5-methyl-7methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (315 mg) was dissolved in 6 ml of THF and 6 ml of water. To the solution was added 368 mg of OXONE (manufactured by Du Pont (E.I.) de Nemours & Co.) under ice cooling. The mixture was stirred at the same temperature for 1.5 hr. An aqueous sodium hydrogencarbonate solution was added thereto, followed by extraction with dichloromethane. The extract was dried over anhydrous magnesium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by column chromatography on silica gel (dichloromethane:methanol=20:1 to 10:1). Of two main components, the fraction, which had been eluted earlier, was concentrated under the reduced pressure to give 145 mg of 4-nitrobenzyl (S,5R,6S)-6-((1R)-1-hydroxyethyl)-2(7-methanesulfonyl-5-methylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate.

NMR (CDCl 3 ) δ: 1.30 (3H, d, J=7.4 Hz), 1.40 (3H, d, J=6.4 Hz), 2.64 (3H, s), 3.19 (3H, s), 3.38 (1H, dd, J 1 =6.7 Hz, J 2 =2.9 Hz), 3.48 (1H, m), 4.40 (1H, dd, J 1 =9.7 Hz, J 2 =2.9 Hz), 5.28 (1H, d, J=14.0 Hz), 5.54 (1H, d, J=14.0 Hz), 7.69 (2H, d, J=8.5 Hz), 8.25 (2H, d, J=8.5 Hz), 8.32 (1H, s).

c) Sodium (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonyl-5-methylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-b), 104 mg of the title compound was obtained from 172 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonyl-5-methylimidazo[5,1 b]thiazol-2-yl)-l-methyl-1-carbapen-2-em-3-carboxylate.

NMR (D 2 O) δ (HOD=4.80 ppm): 1.22 (3H, d, J=7.2 Hz), 1.32 (3H, d, J=6.2 Hz), 2.57 (3H, s), 3.25 (3H, s), 3.50 (1H, m), 3.61 (1H, m), 4.29 (2H, m), 7.84 (1H, s).

›Example 45

Sodium (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonyl-5-methylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

a) 4-Nitrobenzyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonyl-5-methylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

Of the two main components, the fraction, which had been eluted later in the column chromatography on silica gel in Example 44-b), was concentrated under the reduced pressure to give 139 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonyl-5-methylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers).

NMR (CDCl 3 ) δ: 1.29 (3H, m), 1.39 (3H, d, J=6.4 Hz), 2.62 (3H, s), 2.92, 2.94 (total 3H, s each), 3.36 (1H, m), 3.45 (1H, m), 4.32 (2H, m), 5.27 (1H, d, J=13.4 Hz), 5.54 (1H, d, J=13.4 Hz), 7.68 (2H, d, J=8.8 Hz), 8.25 (2H, d, J=8.8 Hz), 8.31 (1H, s).

b) Sodium (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonyl-5-methylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example 1-b), 127 mg of the title compound was obtained from 204 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonyl-5-methylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers).

NMR (D 2 O) δ (HOD=4.80 ppm): 1.23 (3H, d, J=6.9 Hz), 1.32 (3H, d, J=6.3 Hz), 2.56 (3H, s), 3.03 (3H, s), 3.50 (1H, m), 3.59 (1H, m), 4.29 (2H, m), 7.82, 7.85 (total 1H, s each).

›Example 46

1-(Ethoxycarbonyloxy)ethyl (1S,5R,6S)-2-(7-Acetylimidazo[5,1-b]thiazol-2-yl)-6 ((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

a) 4-Nitrobenzyl (1S,5R,6S)-2-7-Acetylimidazo[5,1-b]thiazol-2-yl)-6-(1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 5.93 g of 4-nitrobenzyl (1S,5R,6S)-2-(7-acetylimidazo[5,1-b]thiazol-2-yl)-6((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate was obtained from 1.53 g of 4-nitrobenzyl (1R,3R,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-oxo-1-carbapenam-3-carboxylate and 8.80 g of 7-acetyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 1.31 (3H, d, J=7.4 Hz), 1.40 (3H, d, J=6.2 Hz), 2.61 (3H, s), 3.40 (1H, dd, J 1 =6.6 Hz, J 2 =2.9 Hz), 3.52 (1H, m), 4.32 (1H, m), 4.42 (1H, dd, J 1 =9.7 Hz, J 2 =2.9 Hz), 5.27 (1H, d, J=13.5 Hz), 5.52 (1H, d, J=13.5 Hz), 7.67 (2H, d, J=8.5 Hz), 8.01 (1H, s), 8.22 (2H, d, J=8.5 Hz), 8.50 (1H, s).

b) Sodium (4S,5R,6S)-2-(7-Acetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate.

In the same manner as in Example 1-b), 954 mg of sodium (1S,5R,6S)-2-(7-acetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate was obtained from 1.53 g of 4-nitrobenzyl (1S,5R,6S)-2-(7-acetylimidazo[ 5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate.

NMR (D 2 O) δ (HOD 4.80 ppm): 1.20 (3H, d, J=7.2 Hz), 1.33 (3H, d, J=6.4 Hz), 2.45 (3H, s), 3.50 (1H, dd, J 1 =6.1 Hz, J 2 =2.5 Hz), 3.57 (1H, m), 4.28 (1H, m), 4.33 (1H, dd, J 1 =9.3 Hz, J 2 =2.5 Hz), 7.92 (1H, s), 8.05 (1H, s).

c) 1-(Ethoxycarbonyloxy)ethyl (1S,5R,6S)-2-(7-Acetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

Sodium (1S,5R,6S)-2-(7-acetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (71.9 mg) was dissolved in 2.0 ml of DMF. 1-(Ethoxycarbonyloxy)ethyl iodide (66.3 mg) was added to the solution in an argon atmosphere at −20° C. The mixture was stirred for 2 hr while raising the temperature to −10° C. Ethyl acetate (20 ml) was added to the reaction solution. The mixture was extracted twice, followed by washing twice with 10 ml of semisaturated brine. The organic layer was dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated under the reduced pressure to a volume of 2 ml. The residue was purified by column chromatography on silica gel (chloroform:methanol=15:1) and Sephadex LH-20 (dichloromethane:methanol=1:1) in that order to give 57.4 mg of the title compound.

NMR (CDCl 3 ) δ: 1.28 (3H, d, J=7.2 HZ), 1.32-1.41 (6H, m), 1.60, 1.65 (total 3H, d each, J=5.4 Hz), 2.62 (3H, s), 3.34 (1H, m), 3.49 (1H, m), 4.21 (1H, m), 4.29 (2H, m), 4.39 (1H, m), 6.94 (1H, m), 8.02 (1H, s), 8.61, 8.63 (total 1H, s each); MS (TSP): 492 (M + +H).

›Example 47

1-(Isopropoxycarbonyloxy)ethyl (1S,5R,6s)-2-(7-Acetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example 46, 41.7 mg of the title compound was obtained from 54.8 mg of sodium (1S,5R,6S)-2-(7-acetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate and 100.0 mg of 1-(isopropoxycarbonyloxy)ethyl iodide.

NMR (CDCl 3 ) δ: 1.25-1.40 (12H, m), 1.59, 1.66 (total 3H, d each, J=5.5 Hz), 2.62 (3H, s), 3.34 (1H, m), 3.49 (1H, m), 4.29 (1H, m), 4.38 (1H, m), 4.90 (1H, m), 6.93 (1H, m), 8.03 (1H, m), 8.03(1H, s), 8.43 (1H, m), 8.63, 8.64 (total 1H, s each); MS (TSP): 506 (M + +H).

›Example 48

1-(Cyclohexyloxycarbonyloxy)ethyl (1S,5R,6S)-2-(7-Acetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example 46, 59.4 mg of the title compound was obtained from 58.1 mg of (1S,5R,6S)-2-(7-acetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate sodium and 65.2 mg of 1-(cyclohexyloxycarbonyloxy)ethyl iodide.

NMR (CDCl 3 ) δ: 1.28 (3H, m), 1.38 (3H, m), 1.25-1.82 (8H, m), 1.59, 1.65 (total 3H, d each, J=5.4 Hz), 1.85-2.02 (2H, m), 2.62 (3H, s), 3.32 (1H, m), 3.48 (1H, m), 4.29 (1H, m), 4.38 (1H, m), 4.65 (1H, m), 6.95 (1H, m), 8.01, 8.02 (total 1H, s each), 8.61, 8.63 (total 1H, s each); MS (TSP): 546 (M + +H).

›Example 49

Cyclohexyloxycarbonyloxymethyl (1S,5R,6S)-2-(7-Acetylimidazo[5,1-b]thiazol-2-yl)-6 ((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 46, 68.7 mg of the title compound was obtained from 56.4 mg of sodium (1S,5R,6S)-2-(7-acetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate and 60.5 mg of cyclohexyloxycarbonyloxymethyl iodide.

NMR (CDCl 3 ) δ: 1.28 (3H, d, J=7.1 Hz), 1.37, (3H, d, J=6.2 Hz), 1.25-1.55 (6H, m), 1.68-1.78 (2H, m), 1.83-1.96 (2H, m), 2.62 (3H, s), 3.35 (1H, dd, J 1 =6.6 Hz, J 2 =2.7 Hz), 3.50 (1H, m), 4.30 (1H, m), 4.39 (1H, dd, J 1 =9.7 Hz, J 2 =2.7 Hz), 4.64 (1H, m), 5.87, 5.96 (2H, ABq, J=5.8 Hz), 8.04 (1H, s), 8.57 (1H, s); MS (TSP): 532 (M + +H).

›Example 50

3-Phthalidyl (1S,5R,6S)-2-(7-acetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example 46, 39.7 mg of the title compound was obtained from 56.2 mg of sodium of (1S,5R,6S)-2-(7-acetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate and 60.3 mg of 3-phthalidyl bromide.

NMR (CDCl 3 ) δ: 1.12 (3H, m), 1.22 (3H, m), 2.46 (3H, s), 3.42 (1H, m), 3.75 (1H, m), 3.97 (1H, m), 4.30, (1H, m), 5.10, 5.12 (total 1H, s each), 7.65 (1H, s), 7.74 (1H, m), 7.8.3 (1H, m), 7.93 (1H, m), 8.33, 8.56 (total 1H, s each), 8.39, 8.60 (total 1H, s each); MS (TSP): 508 (M + +H).

›Example 51

1-(Acetoxy)ethyl (1S,5R,6S)-2-(7-Acetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example 46, 79.3 mg of the title compound was obtained from 93.1 mg of sodium (1S,5R,6S)-2(7-acetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate and 118.0 mg of 1-(acetoxy)ethyl iodide.

NMR (CDCl 3 ) δ: 1.20 (3H, d, J=7.2 Hz), 1.31 (3H, m), 1.49, 1.54 (total 3H, d each, J=5.5 Hz), 1.99, 2.07 (total 3H, s each), 2.55 (3H, s), 3.28 (1H, m), 3.42 (1H, m), 4.22 (1H, m), 4.31 (1H, m), 6.98 (1H, m), 7.95, 7.96 (total 1H, s each), 8.53, 8.54 (total 1H, s each); MS (TSP): 462 (M + +H).

›Example 52

(5-Methyl-2-oxo-1,3-dioxolen-4-yl)methyl (1S,5R,6S)-2-(7-Acetylmidazo[5,1-b]thiazol-2-yl)-6((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 46, 94.1 mg of the title compound was obtained from 84.6 mg of sodium (1S,5R,6S)-2-(7-acetylimidazo[5,1-b]thiazol-2-yl-6-((1R)-1-hydroxymethyl)-1-methyl-1-carbapen-2-em-3-carboxylate and 81.3 mg of (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl bromide.

NMR (CDCl 3 ) δ: 1.28 (3H, d, J=17.2 Hz), 1.37 (3H, d, J=6.3 Hz), 2.22 (3H, s), 2.61 (3H, s), 3.45 (1H, dd, J 1 =6.5 Hz, J 2 =2.8 Hz), 3.54 (1H, m), 4.29 (1H, m), 4.39 (1H, dd, J 1 =9.8 Hz, J 2 =2.8 Hz), 5.01, 5109 (2H, ABq, J=13.8 Hz), 8.05 (1H, s), 8.40 (1H, s); MS (TSP): 488 (M + +H).

›Example 53

Sodium (1S,5R,6S)-2-(7-N-Acetylaminomethylimidazo-[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (1S,5R,6S)-2-(7-N-Acetylaminomethylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In substantially the same manner as in Example 1-a), 1.11 g of 4-nitrobenzyl (1S,5R,6S)-2-(7-N-acetylaminomethylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate was obtained from 0.91 g of 4-nitrobenzyl (1R,3R,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-oxo-1-carbapenam-3-carboxylate and 1.09 g of 7-N-acetylaminomethyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (DMSO-d 6 ) δ: 1.15-1.20 (6H, m), 1.86 (3H, s), 3.41 (1H, dd, J 1 =6.0 Hz, J 2 =2.7 Hz), 3.07-3.17 (1H, m), 3.62 (1H, dd, J 1 =8.8 Hz, J 2 =2.7 Hz), 4.00-4.05 (1H, m), 4.16 (2H, d, J=5.8 Hz), 5.13 (1H, d, J=4.9 Hz), 5.39 (1H, d, J=13.8 Hz), 5.48 (1H, d, J=13.8 Hz), 7.71 (2H, d, J=8.5 Hz) 8.22 (2H, d, J=8.5 Hz), 8.21 (1H, s), 8.36 (1H, s), 8.43 (1H, t, J=5.8 Hz).

b) Sodium: 1 (1S,5R,6S)-2-(7-N-Acetylaminomethylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

The title compound (0.52 g) was obtained from 175 mg of 4-nitrobenzyl (1S,5R,6S)-2-(7-N-acetylaminomethylimidazo[5,1-b]thiazlol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate in substantially the same manner as in Example 1-b), except that the purification was carried out using Cosmosil 40C18-PREP (5% aqueous methanol).

NMR (D 2 O) δ (HOD 4.80 ppm): 1.22 (3H, d, J=7.1 Hz), 1.31 (3H, d, J=6.3 Hz), 2.08 (3H, s), 4.,37 (2H, s), 7.82 (1H, s), 8.04 (1H, s).

›Example 54

Pivaloyloxymethyl (1S,5R,6S)-2-(7-N-Acetylaminomethylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-22-em-3-carboxylate

In substantially the same manner as in Example 2, 75 mg of the title compound was obtained from 81 mg of sodium (1S,5R,6S)-2-(7-N-acetylaminomethylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate.

NMR (CDCl 3 ) δ: 1.21 (9H, s), 1.26 (3H, d, J=7.4 Hz), 1.36 (3H, d, J=6.3 Hz), 3.02 (3H, s), 3.32 (1H, d, J 1 =6.6 Hz, J 2 =2.8 Hz), 3.40-3.5.0 (1H, m), 4.25-4.35 (2H, m), 4.39-4.56 (2H, m), 5.87 (1H, d, J=5.6 Hz), 5.98 (1H, d, J=5.6 Hz), 6.30 (1H, s), 7.98 (1H, s), 8.35 (1H, s).

›Example 55

1-(Acetoxy)ethyl (1S,5R,6S)-2-(7-N-Acetylaminomethylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example 46, 14.4 mg of the title compound was obtained from 45.2 mg of sodium (1S,5R,6S)-2-(7-N-acetylaminomethylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate and 90.8 mg of 1-(acetoxy)ethyl iodide.

NMR (CDCl 3 ) δ: 1.26 (3H, m), 1.37 (3H, m), 1.56, 1.61 (total 3H, d each, J=5.5 Hz), 2.02 (3H, s), 2.06, 2.14 (total 3H, s each), 2.10 (1H, s), 3.32 (1H, m), 3.42 (1H, m), 4.26-4.35 (2H, m), 4.40-4.55 (2H, m), 6.25 (1H, m), 7.03 (1H, m), 7.96, 7.97 (total 1H, s each) 8.43, 8.44 (total 1H, s each); MS (TSP): 491 (M + +H).

›Example 56

1-(Cyclohexyloxycarbonyloxy)ethyl (1S,5R,6S)-2-(7-N-Acetylaminomethylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example 46, 46.5 mg of the title compound was obtained from 45.1 mg of sodium (1S,5R,6S)-2-(7-N-acetylaminomethylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate and 63.0 mg of 1-(cyclohexyloxycarbonyloxy)ethyl iodide.

NMR (CDCl 3 ) δ: 1.26 (3H, m), 1.37 (3H, m), 1.38-2.00 (11H, m), 1.59, 1.65 (total 3H, d each, J=5.5 Hz), 2.03 (3H, s), 3.33 (1H, m), 3.42 (1H, m), 4.26-4.38 (2H, m), 4.40-4.55 (2H, m), 4.65 (1H, m), 6.22 (1H, br·s), 6.94 (1H, m), 7.95 (1H, s), 8.43, 8.44 (total 1H, s each); MS (TSP): 575 (M + +H).

›Example 57

3-Phthalidyl (1S,5R,6S)-2-(7-N-Acetylaminomethylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example 46, 27.7 mg of the title compound was obtained from 33.2 mg of sodium (1S,5R,6S)-2-(7-N-acetylaminomethylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate and 33.8 mg of 3-phthalidyl bromide.

NMR (CDCl 3 ) δ: 1.26-1.46 (6H, m), 1.70 (1H, m), 2.03, (3H, s), 3.33 (1H, m), 3.48 (1H, m), 4.15-4.35 (2H, m), 4.38-4.68 (2H, m), 6.22 (1H, m), 7.45, 7.46(total 1H, s each), 7.64-7.81 (3H, m), 7.91-7.98 (1H, m), 8.16, 8.49 (total 1H, s each); MS: (TSP): 537 (M + +H).

›Example 58

(5-Methyl-2-oxo-1,3-dioxolen-4yl)-methyl (1S,5R,6S)-2-(7-N-acetylaminomethylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 46, 25.0 mg of the title compound was obtained from 41.7 mg of sodium (1S,5R,6S)-2-(7-N-acetylaminomethylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate and 40.0 mg of (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl bromide.

NMR (CDCl 3 ) δ: 1.27 (3H, d, J=7.1 Hz), 1.36 (3H, d, J=6.2 Hz), 1.80 (1H, br·s), 2.03 (3H, s), 2.21 (3H, s), 3.33 (1H, dd, J 1 =6.5 Hz, J 2 =2.9 Hz), 3.47 (1H, m), 4.25-4.55 (2H, m), 5.01, 5.07 (2H, ABq, J=14.0 Hz), 6.32 (1H, m), 7.98 (1H, s), 8.20 (1H, s); MS (TSP): 517 (M + +H).

›Example 59

1-[(Cyclohexylmethoxy)carbonyloxy]ethyl (1S,5R,6S)-2-(7-N-Acetylaminomethylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example 46, 12.8 mg of the title compound was obtained from 24.3 mg of sodium (1S,5R,6S)-2-(7-N-acetylaminomethylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate and 71.0 mg of 1-[(cyclohexylmethoxy)carbonyloxy]ethyl iodide.

NMR (CDCl 3 ) δ: 0.92-1.05 (3H, m), 1.16-1.25 (2H, m), 1.26 (3H, m), 1.37 (3H, m), 1.60-1.78 (9H, m), 2.03 (3H, s), 3.31 (1H, m), 3.43 (1H, m), 3.93-4.05 (2H, m), 4.25-4.35 (2H, m), 4.40-4.56 (2H, m), 6.20 (1H, m), 6.92 (1H, m), 7.96 (1H, s), 8.44, 8.45 (total 1H, s each); MS (TSP): 589 (M + +H).

›Example 60

(1R,2S,5R)-(1)-Menthyloxycarbonyloxymethyl (1S,5R,6S)-2-(7-N-Acetylaminomethylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 46, 38.1 mg of the title compound was obtained from 33.3 mg of sodium (1S,5R,6S)-2-(7-N-acetylaminomethylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate and 39.8 mg of (1R,2S,5R)-(1)-menthyloxycarbonyloxymethyl iodide.

NMR (CDCl 3 ) δ: 0.77 (3H, d, J=7.6 Hz), 0.89 (3H, d, J=7.1 Hz), 0.95-1.15 (2H, m), 1.26 (3H, d, J=7.2 Hz), 1.36 (3H, d, J=6.1 Hz), 1.37-1.52 (2H, m), 1.64-1.72 (2H, m), 1.80-2.10 (3H, m), 2.03 (3H, s), 3.32 (1H, dd, J 1 =6.6 Hz, J 2 =2.8 Hz), 3.44 (1H, m), 4.25-4.35 (2H, m), 4.45-4.60 (3H, m), 5.91, 5.94 (2H, ABq, J=5.5 Hz), 6.41 (1H, m), 7.97 (1H, s), 8.40 (1H, s); MS (TSP): 617 (M + +H).

›Example 61

1-(Cyclohexyloxycarbonyloxy)-n-propyl (1S,5R,6S)-2-(7-N-Acetylaminomethylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example 46, 15.9 mg of the title compound was obtained from 30.4 mg of sodium (1S,5R,6S)-2-(7-N-acetylaminomethylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate and 33.3 mg of 1-(cyclohexyloxycarbonyloxy)-n-propyl iodide.

NMR (CDCl 3 ) δ: 0.99, 1.07 (total 3H, t each, J=7.7 Hz), 1.25 (3H, m), 1.36 (3H, m), 1.30-1.80 (8H, m), 1.85-2.05 (4H, m), 2.03 (3H, s), 3.31 (1H, m), 3.43 (1H, m), 4.26-4.35 (1H, m), 4.45-4.50 (1H, m), 4.56-4.72 (1H, m), 6.27 (1H, m), 6.80 (1H, m), 7.94, 7.95 (total 1H, s each), 8.45, 8.47 (total 1H, s each); MS (TSP): 589 (M + +H).

›Example 62

Sodium (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2yl)-1-methyl-1-carbapen-2-em-3-carboxylate

In substantially the same manner as in Example 1-a), 123 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate was obtained from 109 mg of 4-nitrobenzyl (1R,3R,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-oxo-1-carbapenam-3-carboxylate and 141 mg of 7-methanesulfonyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 1.30 (3H, d, J=7.2 Hz), 1.37 (3H, d, J=6.3 Hz), 3.21 (3H, s), 3.36 (1H, dd, J 1 =6.9 Hz, J 2 =2.8 Hz), 3.45-3.55 (1H, m), 4.20-4.30 (1H, m), 4.39 (1H, dd, J 1 =9.6 Hz, J 2 =2.8 Hz), 5.30 (1H, d, J=13.5 Hz), 5.52 (1H, d, J=13.5 Hz), 7.69 (2H, d, J=8.9 Hz), 8.10 (1H, s), 8.24 (2H, d, J=8.9 Hz), 8.43 (1H, s).

b) Sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol 2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

The title compound (83.4 mg) was obtained from 123 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R))-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate, except that the purification was carried out using Cosmosil40C18-PREP (5% aqueous methanol).

NMR (D 2 O) δ (HOD=4.80 ppm): 1.25 (3H, d, J=7.0 Hz), 1.32 (3H, d, J=6.3 Hz), 3.30 (3H, s), 3.52-3.55 (1H, m), 3.55-3.66 (1H, m), 4.24-4.35 (2H, m), 8.03 (1H, s), 8.28 (1H, s).

›Example 63

Pivaloyloxymethyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

In substantially the same manner as in Example 2, 68.5 mg of the title compound was obtained from 54.7 mg of sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate.

NMR (CDCl 3 ) δ: 1.21 (9H, s), 1.28 (3H, d, J=7.3 Hz), 1.34 (3H, d, J=6.3 Hz), 3.23 (3H, s), 3.40 (1H, dd, J 1 =5.8 Hz, J 2 =2.7 Hz), 3.50-3.61 (1H, m), 4.23-4.31 (1H, m), 4.40 (1H, dd, J 1 =9.7 Hz, J 2 =2.7 Hz), 5.87 (1H, d, J=5.7 Hz), 5.98 (1H, d, J=5.7 Hz), 8.25 (1H, s), 8.51 (1H, s).

›Example 64

1-(Acetoxy)ethyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-2-em3-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example 46, 22.2 mg of the title compound was obtained from 55.8 mg of sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate and 50.0 mg of 1-(acetoxy)ethyl iodide.

NMRR (CDCl 3 ) δ: 1.21 (3H, d, J=7.4 Hz), 1.30 (3H, m), 1.50, 1.54 (total 3H, d each, J=5.5 Hz), 2.02, 2.10 (total 3H, s each), 3.28 (1H, m), 3.40 (1H, m), 4.22 (1H, m), 4.30 (1H, m), 6.95 (1H, m) 8.03, 8.04 (total 1H, s each), 8.48 (1H, s); MS (TSP): 498 (M + +H).

›Example 65

1-(Cyclohexyloxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example 46, 19.0 mg of the title compound, was obtained from 24.8 mg of sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate and 52.9 mg of 1-(cyclohexyloxycarbonyloxy)ethyl iodide.

NMR (CDCl 3 ) δ: 1.20 (3H, d, J=7.2 Hz), 1.30 (3H, m), 1.35-1.70 (8H, m), 1.52, 1.58 (total 3H, d each, J=5.4 Hz), 1.80-2.00 (2H, m), 3.15 (3H, s), 3.27 (1H, m), 3.38 (1H, m), 4.20 1H, m), 4.28 (1H, m), 4.58 (1H, m), 6.87 (1H, m), 8.01 (1H, s), 8.49, 8.50 (total 1H, s each); MS (TSP): 582 (M + +H).

›Example 66

3Phthalidyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example 46, 23.5 mg of the title compound was obtained from 27.6 mg of sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate and 30.0 mg of 3-phthalidyl bromide.

NMR (CDCl 3 ) δ: 1.29 (3H, m), 1.32 (3H, m), 2.10 (1H, br.s), 3.21, 3.22 (total 1H, s each), 3.36 (1H, m), 3.50 (1H, m), 4.24 (1H, m), 4.38 (1H, m), 7.44, 7.45 (total 1H, s each), 7.63-7.80 (3H, m), 7.81, 7.91 (total 1H, s each), 8.07, 8.12 (total 1H, s each), 8.32, 8.60 (total 1H, s each); MS (TSP): 544 (M + +H).

›Example 67

(5-Methyl-2-oxo-1,3-dioxolen-4-yl)methyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 46, 17.9 mg of the title compound was obtained from 23.6 mg of sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate and 34.0 mg of (5-methyl-2-oxo-1,3dioxolen-4-yl)methyl bromide.

NMR (CDCl 3 ) δ: 1.29 (3H, d, J=7.4 Hz), 1.37 (3H, d, J=6.3 Hz), 2.22 (3H, s), 3.23 (3H, s), 3.36 (1H, dd, J 1 =6.5 Hz, J 2 =2.8 Hz), 3.49 (1H, m), 4.29 (1H, m), 4.38 (1H, dd, J 1 =9.6 Hz, J 2 =2.8 Hz), 5.02, 5.09 (2H, ABq, J=14.0 Hz), 8.12 (1H, s), 8.34 (1H, s); MS (TSP): 524 (M + +H).

›Example 68

1-[(Cyclohexylmethoxy)carbonyloxy]ethyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example 46, 28.6 mg of the title compound was obtained from 32.2 mg of sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate and 52.5 mg of 1-[(cyclohexylmethoxy)carbonyloxy]ethyl iodide.

NMR (CDCl 3 ) δ: 0.86-1.06 (3H, m), 1.10-1.55 (3H, m), 1.27 (3H, d, J=7.1 Hz), 1.37 (3H, m), 1.60 (3H, d, J=5.5 Hz), 1.58 (3H, d, J=5.5 Hz), 1.60-1.81 (8H, m), 3.21 (3H, s), 3.45 (1H, m), 3.92-4.05 (2H, m), 4.35 (1H, m), 6.93 (1H, m), 8.08, 8.09 (total 3H, s each), 8.56, 8.57 (total 3H, s each); MS (TSP): 596M + +H).

›Example 69

(1-Methylcyclohexan-1-yl)carbonyloxymethyl (1S,5R,6S)-6(1R)-1-Hydroxyethyl)-2-(7-methanesulfonyl-imidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 46, 28.6 mg of the title compound was obtained from 26.3 mg of sodium (1S,5R,6S)-6-((1R) -hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate and 45.0 mg of (1-methylcyclohexan-1-yl)carbonyloxymethyl iodide.

NMR (CDCl 3 ) δ: 1.15 (3H, s), 1.27 (3H, d, J=7.2 Hz), 1.37 (3H, d, J=6.3 Hz), 1.28-1.70 (8H, m), 1.96-2.05 (1H, m), 3.22 (3H, s), 3.35 (1H, dd, J 1 =6.6 Hz, J 2 =2.8 Hz), 3.46 (1H, m), 4.29 (1H, m), 4.36 (1H, dd, J 1 =9.8 Hz, J 2 =2.8 Hz), 5.91, 5.97 (2H, ABq, J=5.6 Hz), 8.11 (1H, s), 8.46 (1H, s); MS (TSP): 566 (M + +H).

›Example 70

1-(Cyclohexyloxycarbonyloxy)-n-propyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example 46, 17.2 mg of the title compound was obtained from 25.0 mg of sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate and 36.0 mg of 1-(cyclohexyloxycarbonyloxy)-n-propyl iodide.

NMR (CDCl 3 ) δ: 1.02, 1.09 (total 3H, t each, J=7.4 Hz), 1.20-2.05 (11H, m), 1.27 (3H, m, 1.36 (3H, m), 3.22 (3H, s), 3.34 (1H, m), 3.48 (1H, m), 4.29 (1H, m), 4.36 (1H, m), 4.65 (1H, m), 6.80 (1H, m), 8.67 (1H, s), 8.59, 8.60 (total 1H, s each); MS (TSP): 596(M + +H).

›Example 71

Sodium (1S,5R,6S)-2-(7-Hydroxyacetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (1S,5R,6S)-2-(7-t-Butyldimethylsilyloxyacetylimidazo[5,1-b]thiazol-2-yl)-6((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 397 mg of 4-nitrobenzyl (1S,5R,6S)-2-(7-t-butyldimethylsilyloxyacetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate was obtained from 567 mg of 4-nitrobenzyl (1R,3R,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-oxo-1-carbapen-3-carboxylate and 1.10 g of 7-t-butyldimethylsilyloxyacetyl-2-(tri-n-butylstannyl)-imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 0.15 (6H, s), 0.96 (9H, s), 1.30 (3H, d, J=7.4 Hz), 1.40 (3H, d, J=6.3 Hz), 3.38 (1H, m), 3.50 (1H, m), 4.32 (1H, m), 4.40 (1H, dd, 1J 1 =9.5 Hz, J 2 =2.9 Hz), 5.08 (2H, s), 5.28 (1H, d, J=14.1 Hz), 5.52 (1H, d, J=14.1 Hz), 7.68 (2H, d, J=8.8 Hz), 7.98 (1H, s), 8.25 (2H, d, J=8.8 Hz), 8.51 (1H, s).

b) 4-Nitrobenzyl (1S,5R,6S)-2-(7-Hydroxyacetylimidazo[5,1-b]thiazol-2-yl)-6-(1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 36-b), 193 mg of 4-nitrobenzyl (1S,5R,6S)2-(7-hydroxyacetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl;)-1-methyl-1-carbapen-2-em-3-carboxylate was obtained from 397 mg of 4-nitrobenzyl (1S,5R,6S)-2-(7-t-butyldimethylsilyloxyacetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate.

NMR (CDCl 3 ) δ: 1.32 (3H, d, J=7.12 Hz), 1.40 (3H, d, J=6.3 Hz), 3.40 (1H, dd, J 1 =6.3 Hz, J 2 =2.8 Hz), 3.51 (2H, m), 4.33 (1H, m), 4.42 (1H, dd, J=9.6 Hz, J 2 =2.8 Hz), 4.91 (2H, d, J=4.4 Hz), 5.28 (1H, d, J=13.7 Hz), 5.53 (1H, d, J=13.7 Hz), 7.68 (2H, J=8.8 Hz), 8.02 (1H, s), 8.24 (2H, d, J=8.8 Hz), 8.51 (1H, s).

c) Sodium (1S,5R,6S)-2-(7-Hydroxyacetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-b), 259 mg of the title compound was obtained from 407 mg of 4-nitrobenzyl (1S,5R,6S)-2-(7-hydroxyacetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate.

NMR (D 2 O) δ (HOD=4.80 ppm): 1.20 (3H, d, J=6.7 Hz), 1.33 (3H, d, J=6.3 Hz), 3.50 (2H, m), 4.30 (2H, m), 4.75 (2H, m), 7.88 (1H, s), 8.02 (1H, s).

›Example 72

Pivaloyloxymethyl (1S,5R,6S)-2-(7-Hydroxyacetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 2, 56.2 mg of the title compound was obtained from 60.4 mg of sodium (1S,5R,6S)-2-(7-hydroxyacetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate.

NMR (CDCl 3 ) δ: 1.20 (9H, s), 1.30 (3H, d, J=7.4 Hz), 1.38 (3H, d, J=6.2 Hz), 3.36 (1H, dd, J 1 =6.7 Hz, J 2 =2.9 Hz), 3.50 (2H, m), 4.30 (1H, m), 4.40 (1H, dd, J 1 =9.9 Hz, J 2 =2.9 Hz), 4.92 (2H, d, J=3.8 Hz), 5.87 (1H, d, J=5.5 Hz), 6.00 (1H, d, J=5.5 Hz), 8.06 (1H, s), 8.51 (1H, s).

›Example 73

1-(Acetoxy)ethyl (1S,5R,6S)-2-(7-Hydroxyacetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

In the same manner as in . . . , the title compound (16.6 mg) was obtained from 25.0 mg of sodium (1S,5R,6S)-2-(7-hydroxyacetylimidazo[5,1-b]thiazol-2-yl -6-((1R)-1-hydroxyethyl)-1-methyl-carbapen-2-em-3-carboxylate and 30.0 mg of 1-(acetoxy)ethyl iodide.

NMR (CDCl 3 ) δ: 1.21 (3H, d, J=7.4 Hz), 1.31 (total 3H, d each, J=6.2 Hz), 1.49, 1.54 (total 3H, d each, J=5.5 Hz), 1.65 (1H, br·s), 2.00, 2.07 (total 3H, s each), 3.28 (1H, m), 3.37-3.50 (2H, m), 4.22 (1H, m), 4.32 (1H, m), 4.84 (1H, s), 4.85 (1H, s), 6.97 (1H, m), 7.97, 7.98 (total 1H, s each), 8.53 (1H, s); MS (FAB + ): 478 (M + +H).

›Example 74

1-(Cyclohexyloxycarbonyloxy)ethyl (1S,5R,6S)-2-(7-Hydroxyacetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example 46, 22.7 mg of the title compound was obtained from 22.0 mg of sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-hydroxyacetylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-1-em-3-carboxylate and 45.0 mg of 1-(cyclohexyloxycarbonyloxy)ethyl iodide.

NMR (CDCl 3 ) δ: 1.10-1.40 (7H, m), 1.53, 1.58 (total 3H, d each, J=5.5 Hz), 1.42-1.75 (4H, m), 1.78-2.00 (6H, m), 2.12 (1H, br·s), 3.28 (1H, m), 3.38-3.50 (2H, m), 4.23 (1H, m), 4.31 (1H, m), 4.59 (1H, m), 4.84 (1H, s), 4.85 (1H, s) 6.87 (1H, m), 7.97 (1H, s), 8.53, 8.54 (total 1H, s each); MS (FAB + ): 562 (M + +H).

›Example 75

3-Phthalidyl (1S,5R,6S)-2-(7-Hydroxyacetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example 46, 24.8 mg of the title compound was obtained from 29.0 mg of sodium (1S,5R,6S)-2-(7-hydroxyacetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate and 29.9 mg of 3-phthalidyl bromide.

NMR (CDCl 3 ) δ: 1.25-1.38 (6H, m), 1.68-1.75 (2H, m), 3.38 (1H, m), 3.52 (1H, m), 4.25 (1H, m), 4.38 (1H, m), 4.91 (1H, s), 4.93 (1H, s), 7.45, 7.46 (total 1H, s each), 7.65-7.82 (3H, m), 7.92-7.95 (1H, m), 8.04, 8.08 (total 1H, s each), 8.41, 8.70 (total 1H, s each); MS (FAB + ): 524 (M + +H).

›Example 76

(5-Methyl-2-oxo-1,3-dioxolen-4-yl)methyl (1S,5R,6S)-2-(7-Hydroxyacetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 46, 23.0 mg of the title compound was obtained from 27.2 mg of sodium (1S,5R,6S)-2-(7-hydroxyacetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate and 30.0 mg of (5-methyl-2-oxo-1,3-dioxolen-4-yl)methylbromide.

NMR (CDCl 3 ) δ: 1.31 (3H, d, J=71.2 Hz), 1.38 (3H, d, J=6.2 Hz), 1.92 (1H, br·s), 2.23 (3H, s), 3.38 (1H, dd, J 1 =6.6 Hz, J 2 =2.9 Hz), 3.49 (1H, br, s), 4.31 (1H, m), 4.40 (1H, dd, J 1 =9.8 Hz,), J 2 =2.9 Hz), 4.91 (1H, s), 4.93 (1H, s), 5.00, 5.06 (2H, ABq, J=14.0 Hz), 8.07 (1H, s), 8.41 (1H, s); MS (FAB + ): 504 (M + +H).

›Example 77

(1-Methylcyclohexan-1-yl)carbonyloxymethyl (1S,5R,6S)-2-(7-Hydroxyacetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 46, 26.4 mg of the title compound was obtained from 20.7 mg of sodium (1S,5R,6S)-2-(7-hydroxyacetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate and 30.0 mg, of (1-methylcyclohexan-1-yl)carbonyloxymethyl iodide.

NMR (CDCl 3 ) δ: 1.14 (3H, s), 1.20-1.60 (9H, m), 1.30 (3H, d, J=7.4 Hz), 1.37 (3H, d, J=6.3 Hz), 1.95-2.05 (2H, m), 3.36 (1H, dd, J 1 =6.5 Hz, J 2 =2.8 Hz), 4.30 (1H, m), 4.40 (1H, dd, J 1 =9.7 Hz, J 2 =2.8 Hz), 4.92 (2H, s), 5.92, 5.98 (2H, ABq, J=5.6 Hz), 8.07 (1H, s), 8.50 (1H, s); MS (TSP): 546 (M + +H).

›Example 78

1-[(Cyclohexylmethoxy)carbonyloxy]ethyl (1S,5R,6S)-2-(7-Hydroxyacetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example 46, 6.12 mg of the title compound was obtained from 21.2 mg of sodium (1S,5R,6S)-2-(7-hydroxyacetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate and 33.0 mg of 1-[(cyclohexylmethoxy)carbonyloxy]ethyl iodide.

NMR (CDCl 3 ) δ: 0.88-1.10 (2H, m), 1.15-1.30 (1H, m), 1.29 (3H, m), 1.38 (3H, m), 1.60, 1.66 (total 3H, d each, J=5.5 Hz), 1.65-1.90, (9H, m), 3.35 (1H, m), 3.50 (1H, m), 3.92-4.05 (2H, m), 4.29 (1H, m), 4.38 (1H, m), 4.91 (1H, s), 4.92 (1H, s), 6.94 (1H, m), 8.03 (1H, s), 8.60, 8.62 (total 1H, s each); MS (TSP): 576 (M + +H).

›Example 79

1-(Cyclohexyloxycarbonyloxy)-n-propyl (1S,5R,6S)-2-(7-Hydroxyacetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example 46, 18.3 mg of the title compound was obtained from 21.7 mg o!f sodium (1S,5R,6S)-2-(7-hydroxyacetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate and 22.0 mg of 1-(cyclohexyloxycarbonyloxy)-n-propyl iodide.

NMR (CDCl 3 ) δ: 1.00, 1.08 (total 3H, t each, J=7.6 Hz), 1.26-1.80 (13H, m), 1.85-2.05 (6H, m), 3.35 (1H, m), 3.50 (2H, m), 4.30 (1H, br.m), 4.39 (1H, m), 4.65 (1H, m), 14.91 (1H, s), 4.92 (1H, s), 6.80, 6.82 (total 1H, d each, J=6.0 Hz), 8.02, 8.03 (total 1H, s each), 8.62, 8.64 (total 1H, s each); MS (TSP): 576 (M + +H).

›Example 80

Sodium (1S,5R,6S)-2-[7-(N,N-dimethylcarbamoyl-1)-acetylimidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (1S,5R,6S)-2-[7-(N,N-dimethylcarbamoyl)acetylimidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate.

In substantially the same manner as in Example 1-a), 245 mg of 4-nitrobenzyl (1S,5R,6S)-2-[7-(N,N-dimethylcarbamoyl)acetylimidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate was obtained from 254 mg of 4-nitrobenzyl (1R,3R,5R,6S)-6-((1R)-1-hydroxyethyl)1-methyl-2-oxo-1-carbapenam-3-carboxylate and 290 mg of 7-(N,N-dimethylcarbamoylacetyl)-2-(tri-n-butylstannyl)-imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 1.30 (3H, d, J=7.2 Hz), 1.37 (3H, d, J=6.2 Hz), 3.07 (3H, s), 3.25 (3H, s), 3.35-3.41 (1H, m), 3.43 (2H, s), 4.18-4.25 (1H, m), 4.35-4.42 (1H, m), 5.31 (1H, d, J=13.5 Hz), 5.52 (1H, d, J=13.5 Hz), 7.30 (1H, s), 7.70 (2H, d, J=8.8 Hz), 8.55 (1H, s,).

b) Sodium (1S,5R,6S)-2-[7-(N,N-dimethylcarbamoyl)acetylimidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

The title compound (143.2 mg ) was obtained from 245 mg of 4-nitrobenzyl (1S,5R,6S)-2-[7-(N,N-dimethylcarbamoyl)acetylimidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate in substantially the same manner as in Example 1-b), except that the purification was carried out using Cosmosil 40C18-PREP (5% aqueous methanol).

NMR (D 2 O) δ (HOD=4.80 ppm): 1.24 (3H, d, J=7.1 Hz), 1.32 (3H, d, J=6.3 Hz), 2.98 (3H, s), 3.10 (3H, s), 3.52 (1H, dd, J 1 =6.1 Hz, J 2 =2.4 Hz), 3.55-3.66 (1H, m), 4.07 (1H, d, J=16.5 Hz), 4.20 (1H, d, J=16.5 Hz), 4.24-4.35 (2H, m), 8.05 (1H, s), 8.17 (1H, s).

›Example 81

Pivaloyloxymethyl (1S,5R,6S)-2-[7-(N,N-dimethylcarbamoyl)acetylimidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In substantially the same manner as in Example 2, 34.1 mg of the title compound was obtained from 48.5 mg of sodium (1S,5R,6S)-2-[7-(N,N-dimethylcarbamoyl)acetylimidazo-[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate.

NMR (CDCl 3 ) δ: 1.21 (9H, s), 1.27 (3H, d, J=7.1 Hz), 1.35 (3H, d, J=6.3 Hz), 3.01 (3H, s), 3.10 (3H, s), 3.27 (1H, dd, J 1 =7.5 Hz, J 2 =2.5 Hz), 3.42-3.53 (1H, m), 4.16 (2H, s), 4.16-4.25 (1H, m), 4.27-4.33 (1H, m), 5.89 (1H, d, J=5.5 Hz), 5.98 (1H, d, J=5.5 Hz), 8.04 (1H, s), 8.55 (1H, s).

›Example 82

(1-Methylcyclohexan-1-yl)carbonyloxymethyl (1S,5R,6S)-2-[7-(N,N-dimethylcarbamoyl)acetylimidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3carboxylate

In the same manner as in Example 46, 25.5 mg of the title compound was obtained from 25.7 mg of sodium (1S,5R,6S)-2-[7-(N,N-dimethylcarbamoyl)acetylimidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate and 31.5 mg of (1-methylcyclohexan-1-yl)carbonyloxymethyl iodide.

NMR (CDCl 3 ) δ: 1.15 (3H, s), 1.22-1.30 (2H, m), 1.25 (3H, d, J=7.4 Hz), 1.36 (3H, d, J=612 Hz), 1.42-1.75 (4H, m), 1.97-2.08 (2H, m), 3.01 (3H s) 3.09 (3H, s), 3.31 (1H, dd, J=7.2 Hz, J 2 =2.8 Hz), 3.48 (1H, m), 4.17 (1H, s), 4.18 (1H, s), 4.23 (1H, m), 4.33 (1H, dd, J 1 =9.7 Hz, J 2 =2.8 Hz), 5.92, 5.97 (2H, ABq, J=5.5 Hz), 8.05 (1H, s), 8.53 (1H, s); MS (TSP): 601 (M + +H).

›Example 83

1-(Cyclohexyloxycarbonyloxy)ethyl (1S,5R,6S)-2-[7-(N,N-dimethylcarbamoyl)acetylimidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example 46, 12.8 mg of the title compound was obtained from 28.2 mg of sodium (1S,5R,6S)-2-[7-(N,N-dimethylcarbamoyl)acetylimidazo[5,1-b]-thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate and 30.0 mg of 1-(cyclohexyloxycarbonyloxy)ethyl iodide.

NMR (CDCl 3 ) δ: 1.22 (3H, d, J=7.4 Hz), 1.35 (3H, m), 1.25-1.80 (9H, m), 1.60, 1.65 (total 3H, d each, J=5.5 Hz), 1.95-2.04 (2H, m), 3.01 (3H, s), 3.09, 3.10 (total 3H, s each), 3.30 (1H, m), 3.47 (1H, m), 4.16, 4.18 (total 2H, s each), 4.25 (1H, m), 4.35 (1H, m), 4.68 (1H, m), 6.94 (1H, m), 8.01, 8.02 (total 1H, s each), 8.63, 8.65 (total 1H, s each); MS (TSP): 617 (M + +H).

›Example 84

3-Phthalidyl (1S,5R,6S)-2-[7-(N,N-dimethyl carbamoyl)acetylimidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example 46, 21.6 mg of the title compound was obtained from 26.0 mg of sodium (1S,5R,6S)-2-[7-(N,N-dimethylcarbamoyl)acetylimidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate and 24.4 mg of 3-phthalidyl bromide.

NMR (CDCl 3 ) δ: 1.24 (3H, m), 1.32 (3H, d, J=6.2 Hz), 3.01 (3 Hz, s), 3.10 (3H, s), 3.31 (1H, m), 3.41 (1H, m), 4.14-4.24 (3H, m), 4.36 (1H, m), 7.44, 7.46 (total 1H, s each), 7.65-7.80 (3H, m), 7.92 (1H, m), 7.99, 8.03 (total 1H, s each), 8.40, 8.67 (total 1H, s each); MS (TSP): 579 (M + +H).

›Example 85

(5-Methyl-2-oxo-1,3-dioxolen-4-methyl (1S,5R,6S)-2-[7-(N,N-dimethylcarbamoyl)acetylimidazo-[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 46, 26.1 mg of the title compound was obtained from 36.1 mg of sodium (1S,5R,6S)-2-[7-(N,N-dimethylcarbamoyl)acetylimidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate and 24.0 mg of (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl bromide.

NMR (CDCl 3 ) δ: 1.27 (3H, d, J=7.1 Hz), 1.37 (3H, d, J=6.2 Hz), 2.22 (3H, s), 2.70 (1H, br·s), 3.01 (3H, s), 3.10 (3H, s), 3.32 (1H, dd, J 1 =7.1 Hz, J 2 =2.8 Hz), 3.50 (1H, m), 4.17 (2H, m), 4.26 (1H, m), 4.38 (1H, dd, J 1 =9.8 Hz, J 2 =2.8 Hz), 5.00, 5.10 (2H, ABq, J=14.2 Hz), 8.04 (1H, s), 8.40 (1H, s); MS (TSP): 559 (M + +H).

›Example 86

1-[(Cyclohexylmethoxy)carbonyloxy)ethyl (1S,5R,6S)-2-[7-(N,N-dimethylcarbamoyl acetylimidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example 46, 22.3 mg of the title compound was obtained from 30.2 mg of sodium (1S,5R,6S)-2-[7-(N,N-dimethylcarbamoyl)acetylimidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate and 45.0 mg of 1-[(cyclohexylmethoxy)carbonyloxy]ethyl iodide.

NMR (CDCl 3 ) δ: 0.92-1.02 (2H, m), 1.10-1.30 (2H, m), 1.23(3H, m), 1.37 (3H, m), 1.60-1.80 (7H, m), 1.60, 1.66 (total 3H, d each, J=5.5 Hz), 3.01 (3H, s), 3.09, 3.10 (total 3H, s each), 3.30 (1H, m), 3.47 (1H, m), 3.47 (1H, m), 3.95-4.04 (2H, m), 4.16-4.35 (4H, m), 6.94 (1H, m), 8.01, 8.02 (total 1H, s each), 8.63, 8.65 (total 1H, s each); MS (TSP): 631 (M + +H).

›Example 87

1-(Cyclohexyloxycarbonyloxy)-n-propyl (1S,5R,6S)-2-[7-(N,N-dimethylcarbamoyl)acetylimidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example 466, 17.9 mg of the title compound Was obtained from 25.1 mg of sodium (1S,5R,6S)-2-[7-(N,N-dimethylcarbamoyl)acetylcarbonylimidazo[5,1-b]thiazol-2-y]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate and 45.0 mg of 1-(cyclohexyloxycarbonyloxy)-n-propyl iodide.

NMR (CDCl 3 ) δ: 0.90-1.40 (3H, m), 1.21 (3H, m), 1.36 (3H, m), 1.45-1.60 (4H, m), 1.85-2.01 (5H, m), 3.01 (1H, s), 3.09 (1H, s), 3.31 (1H, m), 3.49 (1H, m), 3.62 (1H, m), 4.15-4.38 (3H, m), 4.66 (1H, m), 6.80 (1H, m), 8.01, 8.02 (total 1H, s each), 8.64, 8.166 (total 1H, s each); MS (TSP): 631 (M + +H).

›Example 88

Sodium (1S,5R,6S)-2-[7-(N,N-dimethylsulfamoyl)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (1S,5R,6S)-2-[7-(N,N-dimethylsulfamoyl)imidazor5,1-b]thiazol-2-yl]-6-((1R)-1-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In substantially the same manner as in Example 1-a), 115 mg of 4-nitrobenzyl (1S,5R,6S)-2-[7-(N,N-dimethylsulfamoyl)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate was obtained from 109 mg of 4-nitrobenzyl (1R,3R,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-oxo1- carbapenam-3-carboxylate and 143 mg of 7-(N,N-dimethylsulfamoyl)-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 1.30 (3H, d, J=17.2 Hz), 1.37 (3H, d, J=6.1 Hz), 2.84 (6H, m), 3.36 (1H dd, J 1 =6.9 Hz, J 2 =2.5 Hz), 3.50-3.60 (1H, m), 4.20-4.30 (1H, m), 4.38 (1H, dd, J 1 =9.6 Hz, J 2 =2.5 Hz), 5.29 (1H, d, J=13.7 Hz), 5.51 (1H,d, J=13.7 Hz), 7.68 (2H, d, J=8.5 Hz), 8.23 (1H, s), 8.23 (2H, d, J=8.5 Hz), 8.40 (1H, s).

b) Sodium (1S,5R,6S)-2-[7-(N,N-dimethylsulfamoyl)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

The title compound (51.7 mg,) was obtained from 115 mg of 4-nitrobenzyl (1S15R,6S)-2-[7-(N,N-dimethylsulfamoyl)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate in substantially the same manner as in Example 1-b), except that the purification was carried out using Cosmosil 40C18-PREP (10% aqueous methanol).

NMR (D 2 O) δ (HOD=4.80 ppm): 1.25 (3H, d, J=7.1 Hz), 1.31 (3H, d, J=6.0 Hz), 2.77 (6H, s), 3.50-3.55 (1H, m), 3.58-3.66 (1H, m), 4.23-4.36 (2H, m), 8.06 (1H, s), 8.26 (1H, s).

›Example 89

(1S,5R,6s)-2-[7-(N,N-dimethylsulfamoyl)imidazo[5,1-b]thiazol-2-yl]-6-( (1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylatepivaloyloxymethyl

In the same manner as in Example 466, 33.7 mg of the title compound was obtained from 52.2 mg of sodium (1S,5R,6S)-2-[7-(N,N-dimethylsulfamoyl)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate and 45 mg of pivaloyloxymethyl iodide.

NMR (CDCl 3 ) δ: 1.21 (9H, s), 1.29 (3H, d, J=7.4 Hz), 1.37 (3H, d, J=6.3 Hz), 2.88 (6H, s), 3.35 (1H, dd, J 1 =6.5 Hz, J 2 =2.8 Hz), 3.45 (1H, m), 4.29 (1H, m), 4.37 (1H, dd, J 1 =9.8 Hz, J 2 =2.8 Hz), 5.87, 5.99 (2H, ABq, J=5.2 Hz), 8.08 (1H, s), 8.46 (11H, s); MS (TSP): 555 (M + +H).

›Example 90

(1-Methylcyclohexan-1-yl)carbonyloxymethyl 1S,5R,6S)-2-[7-(N,N-dimethylsulfamoyl)imidazo[5,1-b]thiazol2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 46, 34.1 mg of the title compound was obtained from 32.6 mg of sodium (1S,5R,6S)-2-[7 (N,N-dimethylsulfamoyl):imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate and 39.8 mg of (1methylcyclohexan-1-yl)carbonyloxymethyl iodide.

NMR (CDC 3 ) δ: 1.15 (3H, s), 1.210-1.30 (4H, m), 1.27 (3H, d, J=7.2 Hz), 1.36 (3H, d, J=6.3 Hz), 1.41-1.58 (3H, m), 1.97-2.06 (3H, m), 2.87 (6H, s), 334 (1H, dd, J 1 =6.8 Hz, J 2 =2.7 Hz), 3.48 (1H, m), 4.27 (1H, m), 4.36 (1H, dd, J 1 7.4 Hz, J 2 =2.7 Hz), 5.92, 5.97 (2H, ABq, J=5.6 Hz), 8.11 (1H, s), 8.43 (1H, s); MS (TSP): 595 (M + +H).

›Example 91

1-(Cyclohexyloxycarbohyloxy)ethyl (1S,5R,6S)-2-[7-(N,N-dimethylsulfamoyl)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example 46, 17.1 mg of the title compound was obtained from 1.9 mg of sodium (1S,5R,6S)-2-[7-(N,N-dimethylsulfamoyl)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate and 30 mg of 1-(cyclohexyloxycarbonyloxy)ethyl iodide.

NMR (CDCl 3 ) δ: 1.28-1.45 (8H, m), 1.48-1.98 (9H, m), 1.58, 1.65 (total 3H, d each, J=5.5 Hz), 2.87 (6H, s), 3.34 (1H, m), 3.44 (1H, m), 3.62 (1H, m), 4.29 (1H, m), 4.36 (1H, m), 4.66(1H, m), 6.95 (1H, m), 8.05, 8.106 (total 1H, s each), 8.55, 8.56 (total 1H, s each); MS (TSP): 611 (M + +H).

›Example 92

3-Phthalidyl (1S,5R,6s)-2-[7-(N,N-dimethylsulfamoyl)imidazo 5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example 46, 30.7 mg of the title compound was obtained from 32.1 mg of sodium (1S,5R,6S)-2-[7-(N,N-dimethylsulfamoyl)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate and 30.9 mg of 3-phthalidyl bromide.

NMR (CDCl 3 ) δ: 1.25-1.36 (6H, m), 2.20-2.40 (1H, br·s), 2.85 (3H, s), 2.87 (3H, s), 3.36 (1H, m), 3.54 (1H, m), 4.23 (1H, m), 4.38 (1H, m), 7.45, 7.46 (total 1H, s each), 7.65-7.82 (3H, m), 7.90, 7.93 (total 1H, s each), 8.05, 8.09 (total 1H, s each), 8.30, 8.55 (total 1H, s each); MS (TSP): 573 (M + +H).

›Example 93

(5-Methyl-2-oxo-1,3-dioxolen-4-yl)methyl (1S,5R,6S)-2-[7-(N,N-dimethylsulfamoyl)imidazo[5.1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)l-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 46, 38.1 mg of the title compound was obtained from 32.0 mg of sodium (1S,5R,6S)-2-[7-(N,N-dimethylsulfamoyl)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate and 26.0 mg of (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl bromide.

NMR (CDCl 3 ) δ: 1.29 (3H, d, J=7.1 Hz), 1.37 (3H, d, J=6.1 Hz), 2.22 (3H, s), 2.30 (1H, br·s), 2.07 (6H, s), 3.35 (1H, dd, J 1 =6.6 Hz, J 2 =2.8 Hz), 3.50 (1H, m), 4.26-4.33 (1H, m), 4.37 (1H, dd, J 1 =9.6 Hz, J 2 =2.8 Hz), 5.02, 5.10 (2H, ABq, J=14.0 Hz), 8.10 (1H, s), 8.34 (1H, s); MS (TSP): 553 (M+H).

›Example 94

(Cyclohexylmethoxy)carbonyloxy]ethyl (1S,5R,6S)-2-[7-(N,N-dimethylsulfamoyl)imidazo[5,1-b]thiazol-2-yl]-6((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example46, 14.5 mg of the title compound was obtained from 32.0 mg of sodium (1S,5R,6S)-2-[7-(N,N-dimethylsulfamoyl)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate and 45.0 mg of 1-[(cyclohexylmethoxy)carbonyloxy]ethyl iodide.

NMR (CDCl 3 ) δ: 0.95-1.08 (2H, m), 1.15-1.30 (2H, m), 1.27 (3H, d, J=7.4 Hz), 1.37, 1.39 (total 3H, d each, J=6.1 Hz), 1.60, 1.66 (total 3H, d each, J=5,5 Hz), 1.60-1.80 (9H, m), 2.87 (6H, s), 3.33 (1H, m), 3.45 (1H, m), 3.96 (1H, m), 4.02 (1H, d, J=2.1 Hz), 4.28 (1H, m), 4.36 (1H, m), 6.93(1H, m), 8.05, 8.0.6 (total 1H, s each), 8.54, 8.57 (total 1H, s each); MS (TSP): 625 (M + +H).

›Example 95

1-(cyclohexyloxycarbonyloxy)-n-propyl (1S,5R,6S)-2-[7-(N,N-dimethylsulfamoyl)imidazo[5,1-b]thiazol-2-yl]-6-((4R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers

In the same manner as in Example 46, 32.8 mg of the title compound was obtained from 31.5 mg of sodium (1S,5R,6S)-2-[7-(N,N-dimethylsulfamoyl)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate and 45.0 mg of 1-(cyclohexyloxycarbonyloxy)-n-propyl iodide.

NMR (CDCl 3 ) δ: 1.00, 1.08 (total 3H, t each, J=7.4 Hz), 1.26-1.40 (7H, m), 1.45-1.65 (3H, m), 1.70-1.82 (3H, m), 1.85-2.05 (6H, m), 2.88 (6H, s), 3.33 (1H, m), 3.45 (1H, m), 3.61 (1H, m), 4.27 (1H, m), 4.36 (1H, m), 4.65 (1H, m), 6.79, 6.81 (total 1H, t each, J=5.7 Hz), 8.05, 8.06 (total 1H, s each), 8.55, 8.57 (total 1H, s each); MS (TSP): 625 (M + +H).

›Example 96

Sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methoxycarbonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methoxycarbonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 303 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methoxycarbonylimidazo[5,1-b]thiazol-i2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate, was obtained from 467 mg of 4-nitrobenzyl (1R,3R,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-oxo-1-carbapenam-3-carboxylate and 729 mg of methyl 2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole-7-carboxylate.

NMR (CDCl 3 ) δ: 1.32 (3H, d, J=7.3 Hz), 1.40 (3H, d, J=7.6 Hz), 2.00-2.12 (1H, broad), 3.39 (1H, dd, J 1= 6.6 Hz, J 2 =2.9 Hz), 3.51 (1H, dq, J=9.5 Hz, J 2 =7.3 Hz), 3.96 (3H, s), 4.29-4.37 (1H, m), 4.41 (1H, dd, J 1 =9.7 Hz, J 2 =2.9 Hz), 5.28 (1H, d, J=13.7 Hz), 5.52 (1H, d, J=13.7 Hz), 7.68 (2H, dm, J=8.8 Hz), 8.02 (1H, s), 8.24 (2H, dm, J=8.8 Hz), 8.44 (1H, s).

b) Sodium (1S,5R,6S)-6-((1R)-t-hydroxyethyl)-2-(7-methoxycarbonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-b), 188 mg of the title compound was obtained from 3031 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2(7-methoxycarbonyl-imidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate.

NMR (D 2 O) δ (HOD=4.80 ppm): 1.21 (3H, d, J=7.1 Hz), 1.32 (3H, d, J=6.2 Hz), 3.50 (1H, dd, J 1 =6.0 Hz, J 2 =2.6 Hz), 3.58 (1H, qd, J 1 =7.1 Hz, J 2 =6.0 Hz), 4.28 (1H, p, J=6.2 Hz), 4.34 (1H, dd, J 1 =9.2 Hz, J 2 =2.6 Hz), 7.87 (1H, s), 8.07 (1H, s).

›Example 97

Sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-[7-(N-methoxy-N-methylsulfamoyl)imidazo[5,1-b]thiazol-2-yl]-1-methyl-1-carbapen-2-em-3-carboxylate.

a) 4-Nitrobenzyl (i1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-[7-(N-methoxy-N-methylsulfamoyl)imidazo-[5,1-b]thiazol-2-yl]-1-methyl-1-carbapen-2-em-3-carboxylate

In substantially the same manner as in Example 1-a), 160 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-[7-(N-methoxy-N-methylsulfamoyl)imidazo-[5,1-b]thiazol-2-yl]-1-methyl-1-carbapen-2-em-3-carboxylate was obtained from 217 mg of 4-nitrobenzyl (1R,3R,5R,6S)-6-((1R) 1-hydroxyethyl)-1-methyl-2-oxo-1-carbapenam-3-carboxylate and 292 mg of 7-(N-methoxy-N-methylsulfamoyl)-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 1.31 (3H, d, J=7.2 Hz), 1.39 (3H, d, J=6.2 Hz), 3.05 (3H, s), 3.35-3.45 (1H, m), 3.37-3.44 (1H, m), 3.82(1H, s), 4.25-4.35 (1H, m), 4.42 (1H, dd, J 1 =9.8 Hz, J 2 =2.9 Hz), 5.30 (1H, d, J=13.7 Hz), 5.52 (1H, d, J=13.7 Hz), 7.68 (2H, d, J=8.9 Hz), 8.109 (1H, s), 8.24 (2H, d, J=8.9 Hz), 8.43 (1H, s).

b) Sodium (1S,5R,6S)-6-((1R)-f-hydroxyethyl)-2-[7-(N-methoxy-N-methylsulfamoyl)imidazo[5,1-b]thiazol-2-yl]-1-methyl-1-carbapen-2-em-3-carboxylate

The title compound (98 mg) was obtained from 160 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-[7-(N-methoxy-N-methylsulfamoyl)imidazo[5,1-b]thiazol-2-yl]-1-methyl-1-carbapen-2-em-3-carboxylate in substantially the same manner as in Example 1-b), except that the 1 purification was- carried out using Cosmosil 40C18-PREP (10% aqueous methanol).

NMR (D 2 O) δ (HOD=4.80 ppm): 1.25 (3H, d, J=7.3 Hz), 1.31 (3H, d, J=6.4 Hz), 2.95 (3H, s), 3.52 (1H, dd, J 1 =6.8 Hz, J 2 =2.4 Hz), 3.58-3.68 (1H, s), 3.78 (3H, s), 4.24-4.33 (2H, m), 8.10 (1H, s), 8.28 (1H s).

›Example 98

Sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-trifluoroacetylimidazo[5.1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl 1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-trifluoroacetylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

In substantially the same manner as in Example 1-a), 68 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-trifluorolacetylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate was obtained from 109 mg of 4-nitrobenzyl (1R,3R,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-oxo-1-carbapenam-3-carboxylate and 136 mg of 7-trifluoroacetyl-2-(tri-n-_butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 1.32 (3H, d, J=7.3 Hz), 1.40 (3H, d, J=6.2 Hz), 3.38-3.42 (1H, m), 3.50-3.60 (1H, m), 4.30-4.40 (1H, m), 4.43 (1H, dd, J 1 =9.7 Hz, J 2 =2.8 Hz), 5.23-5.38 (1H, m), 5.53 (1H, d, J=13.5 Hz), 7.70 (2H, d, J=8.9 Hz), 8.13 (1H, s), 8.25 (2H, d, J=8.9 Hz), 8.53 (1H, s).

b) Sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-trifluoroacetylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

The title compound (20.6 mg) was obtained from 68 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-trifluoroacetylimidazo[5,1 b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate in substantially the same manner as in Example 1-b), except that the purification was carried out using Cosmosil 40C18-PREP (15% aqueous methanol).

NMR (D 2 O) δ (HOD=4.80 ppm): 1.23 (3H, d, J=7.1 Hz), 1.32 (3H, d, J=6.4 Hz), 3.53 (1H, dd, J 1 =6.1 Hz, J 2 =2.8 Hz), 3.60-3.70 (1H, m), 4.25-4.40 (2H, (1H, s), 8.26 (1H, s).

›Example 99

Sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl 2-(7-sulfamoylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (1S,5R,6S)-2-(7-t-butyldimethylsilylsulfamoylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In substantially the same manner as in Example 1-a), 197 mg of 4-nitrobenzyl (1S,5R,6S)-2-(7-t-butyldimethylsilylsulfamoylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate was obtained from 217 mg of 4-nitrobenzyl (1R,3R,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-oxo-1-carbapenam-3-carboxylate and 303 mg of 7-(t-butyldimethylsilylsulfamoyl)-2-(tri-n-butylstannyl)-imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 0.24 (3H, s), 0.26 (3H, s), 0.93 (9H, s), 1.31 (3H, d, J=7.1 Hz), 1.41 (3H, d, J=6.3 Hz), 3.40 (1H, dd, J 1 =6.3 Hz, J 2 =2.7 Hz), 3.45-3.52 (1H, m), 4.30-4.36 (1H, m), 4.40 (1H, dd, J 1 =9.7 Hz, J 2 =2.7 Hz), 4.57 (1H, s), 5.30 (1H, d, J=13.7 Hz), 5.55 (1H, d, J=13.7 Hz), 7.70 (2H, d, J=8.3 Hz), 8.03 (1H, s), 8.26 (2H, d, J=8.3 Hz), 8 .47 (1H, s).

b) Sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-sulfamoylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

Acetic acid (0.26 ml) and 1.5 ml of a 1 M-tetra-n-butylammonium fluoride/THF solution were added under ice cooling to a solution of 197 mg of 4-nitrobenzyl (1S,5R,6S)-2-(7-t-butyldimethylsilylsulfamoylimidazo-[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate in 6 ml of THF. The solution was stirred at room temperature for 3 hr. The reaction mixture was added to an aqueous sodium hydrogencarbonate solution, followed by extraction with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate. The solvent was removed by distillation. The residue was purified by column chromatography on silica gel (dichloromethane : methanol=10 : 1) to give a crude product of 4-nitrobenzyl (1S,5R,6S)-:6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-sulfamoylimidazo[5,1-b]thiazol-2-yl)-1-carbapen 2-em-3-carboxylate. The crud crude product was dissolved in 5 ml of THF and 5 ml of 1/15 M sodium phosphate buffer (pH 6.6). 10%Pd-C (50 mg) was added thereto. The atmosphere in the reactor was replaced with hydrogen. The system was stirred at room temperature for 30 min. The catalyst; was removed by filtration through Celite, followed by washing with water. The filtrate was adjusted to pH 7.0 by the addition of an aqueous sodium hydrogencarbonate solution, and washed with ethyl acetate. Purification was then carried out using Cosmosil 40C18-PREP (30% aqueous methanol) and Dowex 50 (sodium form) in that order to give 40.7 mg of the title compound.

NMR (D 2 O) δ (HOD=4.80 ppm): 1.26 (3H, d, J=7.4 Hz), 1.32 (3H, d, J=6.3 Hz), 3.53 (1H, dd, J 1 =6.0 Hz, J 2 =2.7 Hz), 3.56-3.68 (1H, m), 4.25-4.35 (2H, m), 8.04 (1H, s), 8.23 (1H, s).

›Example 100

Sodium (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-[7-(2(E)-methoxycarbonylvinyl)imidazo[5,1-b]thiazol-2-yl]-1-methyl-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl(1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-[7-(2-(E)-methoxycarbonylvinyl)imidazo-[5,1-b]thiazol-2-yl]-1-methyl-1-carbapen-2-em-3-carboxylate and 4-Nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-[7-(2-Z)-methoxycarbonylvinyl)imidazo-[5,1-b]thiazol-2-yl]-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 88 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-[7-(2-(E)-methoxycarbonylvinyl)imidazo[5,1-b]thiazol-2-yl]-1-methyl-1-carbapen-2-em-3-carboxylate and 28 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-[7-(2-(Z)-methoxycarbonylvinyl)imidazo[5,1-b]thiazol-2-yl]-1-methyl-1-carbapen-2-em-3-carboxylate were obtained from 320 mg of 4-nitrobenzyl (1R,3R,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-oxo-1-carbapenam-3-carboxylate and 400 mg of 7-(2-methoxycarbonylvinyl)2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole (a mixture of geometrical isomers).

4-Nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-[7-(2-(E)-methoxycarbonylvinyl)imidazo[5,1-b]thiazol-2-yl]-1-methyl-1-carbapen-2-em-3-carboxylate.

NMR (CDCl 3 ) δ: 1.32 (3H, d, J=7.3 Hz), 1.41 (3H, d, J=6.3 Hz), 3.39 (1H, dd, J 1 =6.3 Hz, J 2 =2.7 Hz), 3.51 (1H, m), 3.81 (3H, s), 4.33 (1H, m), 4.40 (1H, dd, J 1 =9.7 Hz, J 2 =2.9 Hz), 5.29, (1H, d, J=13.6 Hz), 5.53 (1H, d, J=13.6 Hz:), 6.18 (1H, d, J=15.9 Hz), 7.69 (2H, d, J=8.7 Hz), 7.73 (1H, d, J=15.9 Hz), 8.06 (1H, s), 8.25 (2H, d, J=8.7 Hz), 8.36 (1H, s).

4-Nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-[7-(2-(Z)-methoxycarbonylvinyl)imidazlo[5,1-b]thiazol-2-yl]-1-methyl-1-carbapen-2-em-3-carboxylate.

NMR (CDCl 3 ) δ: 1.31 (3H, d, J=7.3 Hz), 1.40 (3H, d, J=6.3 Hz), 3.37 (1H, dd, J 1 =6.3 Hz, J 2 =2.7 Hz), 3.58 (1H, m), 3.81 (3H, s), 4.32 (1H, m), 4 38 (1H, dd, J 1 =9.7 Hz, J 2 =2.9 Hz), 5.27 (1H, d, J=13.6 Hz), 5.52 (1H, d, J=13.6 Hz), 5.84 (1H, d, J=12.4 Hz), 7.12 (1H, d, J=12.4 Hz), 7.67 (2H, d, J=8.8 Hz), 8.07 (1H, s), 8.24 (2H, d, J=8.8 Hz), 8.42 (1H, s).

b) Sodium (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-[7-(2-(E)-methoxycarbonylvinyl)imidazo[5,1-b]thiazol-2-yl]-1-methyl-1-carbapen-2-em-3-carboxylate.

In the same manner as in Example 1-b), 37 mg of the title compound was obtained from 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-[7-(2-(E)-methoxycarbonylvinyl)imidazo[5,1-b]thiazol-2-yl]-1-carbapen-2-em-3-carboxylate.

NMR (D 2 O) δ (HOD=4.80 ppm): 1.25 (3H, d, J=7.3 Hz), 1.35; (3H, d, J=6.3 Hz), 3.52 (1H, dd, J 1 6.3 Hz, J 2 =2.4 Hz), 3.60 (1H, m), 3.81 (3H, s), 4.30 (1H, m), 4.33 (1H, dd, J 1 =9.5 Hz, J 2 =2.4 Hz), 5.85 (1H, d, J=15.8 Hz), 7.51 (1H, d, J=15.8 Hz), 7.92 (1H, s), 8.11 (1H, s).

›Example 101

Sodium (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-[7-(2-(Z)-methoxycarbonylvinyl)imidazo[5,1-b]thiazol-2-yl]-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-b), 9.8 mg of the title compound was obtained from 4-nitrobenzyl (1S,5R,65)-6-((1R)-1-hydroxyethyl)-2-[7-(2-(Z)-methoxycarbonylvinyl)imidazo[5,1-b]thiazol-2-yl]-1-methyl-1-carbapen-2-em-3-carboxylate.

NMR (D 2 O) δ (HOD=4.80 ppm): 1.25 (3H, d, J=7.3 Hz), 1.33 (3H, d, J=6.3 Hz), 3.52 (1H, dd, J 1 =6.3 Hz, J 2 =2.4 Hz), 3.57 (1H, m), 3.87 (3H, s), 4.29 (1H, m), 4.32 (1H, dd, J 1 =9.3 Hz, J 2 =2.4 Hz), 5.88 (1H, d, J=12.5 Hz), 7.02 (1H, d, J=12.5 Hz), 7.97 (1H, s), 8.18 (1H, s).

›Example 102

Sodium (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-1-methyl-2-[7-(thiazol-4-yl)imidazo[5,1-b]thiazol-2-yl]-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-1-methyl-2-[7-(thiazol-4-yl)imidazo[5,1-b]thiazol-2-yl]-1-carbapen-2-carboxylate

In the same manner as in Example 1-a), 17 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-[7-(thiazol-4-yl)imidazo[5,1-b]thiazol-2-yl]-1-carbapen-2-em-3-carboxylate was obtained from 224 mg of 4-nitrobenzyl (1R,3R,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-oxo-1-carbapenam-3-carboxylate and 289 mg of 7-(thiazol-4-yl)-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 1.33 (3H, d, J=7.4 Hz), 1.41 (3H, d, J=6.1 Hz), 3.38 (1H, dd, J 1 =6.5 Hz, J 2 =2.8 Hz), 3.50 (1H, m), 4.32 (1H, m), 4.36 (1H, dd, J 1 =94 Hz, J 2 =2.8 Hz), 5.28 (1H, d, J=13.5 Hz), 5.53 (1H, d, J=13.5 Hz), 7.65 (2H, d, J=2.1 Hz), 7.68 (2H, d, J=8.8 Hz), 8.07 (1H, s)8.24 (2H, d, J=8.8 Hz), 8.48 (1H, s), 8.88 (2H, d, J=2.1 Hz); MS: (FAB + ): 552 (M + +H).

b) Sodium (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-1-methyl-2-[7-(thiazol-4-yl)imidazo[5-b]thiazol-2-yl]carbapen-2-em-3-carboxylate

In the same manner as in Example 1-b), 7.0 mg of the title compound was obtained from 16.5 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-[7-(thiazol-4-yl)imidazo[5,1-b]thiazol-2-yl]-1-carbapen-2-em-3-carboxylate.

NMR (D 2 O) δ (HOD=4.80 ppm): 1.20 (3H, t, J=6.9 Hz), 1.34 (3H, d, J=6.4 Hz), 3.45 (1H, m), 3.48 (1H, m), 4.26 (1H, m), 4.30 (1H, m), 7.35 (1H, s), 7.76 (1H, s), 7.91 (1H, s), 8.91 (1H, s).

›Example 103

Sodium (1S,5R,6S)-2-(7-Hydroxyacetyl-5-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (1S,5R,6S)-2-(7-t-Butyldimethylsilyloxyacetyl-5-methylimidazo[5,1-]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 193 mg of 4-nitrobenzyl (1S,5R,6S)-2-(7-t-butyldimethylsilyloxyacetyl-5-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate was obtained from 204 mg of 4-nitrobenzyl (1R,3R,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-oxo-1-carbapenam-3-carboxylate and 405 mg of 7-t-butyldimethylsilyloxyacetyl-5-methyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 0.15 (6H, s), 0.96 (9H, s), 1.30 (3H, d, J=7.4 Hz), 1.40 (3H, d, J=6.2 Hz), 2 64 (3H, s), 3.38 (1H, dd, J 1 =6.5 Hz, J 2 =2.8 Hz), 3.49 (1H, m), 4.31 (1H, m), 4.40 (1H, dd, J 1 =9.5 Hz, J 2 =218 Hz), 5.03 (2H, s), 5.27 (1H, d, J=13.7 Hz), 5.53 (1H, d, J=13.7 Hz), 7.68 (2H, d, J=8.5 Hz), 8.24 (2H, d, J=8.5 Hz), 8.37 (1H, s)

b) 4-Nitrobenzyl (1S,5R,6S)-2-Hydroxyacetyl-5-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 36-b), 122 mg of 4-nitrobenzyl (1S,5R,6S)-2-(7-hydroxyacetyl-5-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate was obtained from 193 mg of 4-nitrobenzyl (1S,5R,6S)-2-(7-t-butyldimethylsilyloxyacetyl-5-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate.

NMR (CDCl 3 ) δ: 1.31 (3H, d, J=7.2 Hz), 1.40 (3H, d, J=6.3 Hz), 2.65 (3H, s), 3.39 (1H, dd, J 1 =6.4 Hz, J=2.7 Hz), 3.52 (2H, m), 4.33 (1H, m), 4.42 (1H, dd, J 1 =9.6 Hz, J 2 =2.7 Hz), 4.85 (2H, s), 5.28 (1H, d, J=13.7 Hz), 5.54 (1H, d, J=13.7 Hz), 7.68 (2H, d, J=8.5 Hz), 8.24 (2H, d, J=8.5 Hz), 8.36 (1H, s).

c) Sodium (1S,5R,6S)-2-(7-Hydroxyacetyl-5-methylimidazo[5.1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-b), 75.9 mg of the title compound was obtained from 122 mg of 4-nitrobenzyl (1S,5R,65)-2-(7-hydroxyacetyl-5-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate.

NMR (D 2 O) δ (HOD=4.80 ppm): 1.19 (3H, d, J=7.2 Hz), 1.33 (3H, d, J=6.3 Hz), 2.48 (3H, s), 3.48 (1H, dd, J 1 =6.1 Hz, J 2 =2.5 Hz), 3.55 (1H, m), 4.30 (2H, m), 4.70 (2H, s), 7.73 (1H, s).

›Example 104

Sodium (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonyl-5-methylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(5-methyl-7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 866 mg of 4-nitrobenzyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(5-methyl-7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate was obtained from 1.04 g of 4-nitrobenzyl (3R,5R,6S)-6-((1R)-1-hydroxyethyl)-2-oxo-1-carbapenam-3-carboxylate and 1.70 g of 5-methyl-7-methylthio-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 1.46 (3H, d, J=6.3 Hz), 2.40 (3H, s), 2.58 (3H, s), 3.33 (3H, m), 4.31 (2H, m), 5.31 (1H, d, J=14.0 Hz), 5.56 (1H, d, J=14.0 Hz), 7.70 (2H, d, J=8.9 Hz), 8.04 (1H, s), 8.25 (2H, d, J=8.9 Hz)

b) 4-Nitrobenzyl (5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonyl-5-methylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

A reaction was carried out in the same manner as in Example 44-b), except that 279 mg of 4-nitrobenzyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(5-methyl-7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate was used as the starting compound. The reaction product was purified by column chromatography on silica gel (dichloromethane:methanol=20:1 to 10:1). Of two main components, the fraction, which had been eluted earlier, was concentrated under the reduced pressure to give 91 mg of 4-nitrobenzyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonyl-5-methylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate.

NMR (CDCl 3 ) δ: 1.40 (3H, d, J=6.4 Hz), 2.63 (3H, s), 3.18 (3H, s), 3.35 (3H, m), 4.34 (2H, m), 5.32 (1H, d, J=13.6 Hz), 5.56 (1H, d, J=13.6 Hz), 7.70 (2H, d, J=9.1 Hz), 8.17 (1H, s), 8.25 (2H, d, J=9.1 Hz).

c) Sodium (5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonyl-5-methylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-b), 45.6 mg of the title compound was obtained from 91 mg of 4-nitrobenzyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonyl-5-methylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate.

NMR (D 2 O) δ (HOD=4.80 ppm): 1.31 (3H, d, J=6.3 Hz), 2.54 (3H, s), 3.24 (3H, s), 3.26 (2H, m), 3.51 (2H, m), 4.26 (2H, m), 7.66 (1H, s).

›Example 105

Sodium (5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfinyl-5-methylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

a) 4-Nitrobenzyl (5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfinyl-5-methylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

Of the two main components, the fraction, which had been eluted later in the column chromatography on silica gel in Example 104-b), was concentrated under the reduced pressure to give 136 mg of 4-nitrobenzyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfinyl-5-methylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers).

NMR (CDCl 3 ) δ: 1.39 (3H, d, J=6.2 Hz), 2.60 (3H, s), 2.94 (3H, s), 3.31 (3H, m), 4.30 (2H, m), 5.29 (1H, d, J=13.7 Hz), 5.53 (1H, d, J=13.7 Hz), 7.68 (2H, d, J=8.6 Hz), 8.10 (1H, m), 8.23 (2H, d, J=81.6 Hz).

b) Sodium (5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfinyl-5-methylimidazo[5.1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example 1-b), 71.8 mg of the title compound was obtained from 136 mg of 4-nitrobenzyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfinyl-5-methylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers).

NMR (D 2 O) δ (HOD=4.80 ppm): 1.31 (3H, d, J=6.5 Hz), 2.57 (3H, s), 3.05 (3H, s), 3.31 (2H, m), 3.52 (1H, m), 4.26 (2H, m), 7.74 (1H, s).

›Example 106

Sodium (5R,6S)-2-(7-Hydroxyacetyl-5-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (5R,6S)-2-(7-t-Butyldimethylsilyloxyacetyl-5-methylimidazo[5,1-2-yl,)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 190 mg of 4-nitrobenzyl (5R,6S)-2-(7-t-butyldimethylsilyloxyacetyl-5-methylimidazo[5,1-b]thiazol-2-yl)-6((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate was obtained from 196 mg of 4-nitrobenzyl (3R,5R,6S)-6-((1R)-hydroxyethyl)-2-oxo-1-carbapenam-3-carboxylate and 405 mg of 7-t-butyldimethylsilyloxyacetyl-5-methyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 0.15 (6H, s), 0.96 (9H, s), 1.40 (3H, d, J=6.1 Hz), 2.63 (3H, s), 3.35 (3H, m), 4.34 (2H, m), 5.03 (2H, s), 5.31 (1H, d, J=13.5 Hz), 5.55 (1H, d, J=13.5 Hz), 7.69 (2H, d, J=8.3 Hz), 8.24 (2H, d, J=8.3 Hz), 8.28 (1H, s).

b) 4-Nitrobenzyl (5R,6S)-2-(7-Hydroxyacetyl-5-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 36-b), 75.9 mg of 4-nitrobenzyl (5R,6S)-2-(7-hydroxyacetyl-5-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate was obtained from 190 mg of 4-nitrobenzyl (5R,6S)-2-(7-t-butyldimethylsilyloxyacetyl-5-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate.

NMR (CDCl 3 ) δ: 1.40, (3H, d, J=6.3 Hz), 2.65 (3H, s), 3.35 (3H, m), 3.57 (1H, t, J=5.0 Hz), 4.35 (2H, m), 4.85 (2H, d, J=5.0 Hz), 5.33 (1H, d, J=13.7 Hz), 5.56 (1H, d, J=13.7 Hz), 7.70 (2H, d, J=8.5 Hz), 8.25 (1H, s), 8.25 (2H, d, J=8.5 Hz).

c) Sodium (5R,6S)-2-(7-Hydroxyacetyl-5-methylimidazo-5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-b), 34.0 mg of the title compound was obtained from 75.9 mg of 4-nitrobenzyl (5R,6S)-2-(7-hydroxyacetyl-5-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate.

NMR (D 2 O) δ (HOD=4.80 ppm): 1.33 (3H, d, J=6.3 Hz), 2.41 (3H, s), 3.16 (2H, m), 3.49 (1H, dd, J 1 =5.6 Hz, J 2 =2.5 Hz), 4.23 (2H, m), 4.68 (2H, s), 7.52 (1H, s).

›Example 107

Pivaloyloxymethyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonyl-5-methylimidazo[5,1-]thiazol-2yl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 2, 26.5 mg of the title compound was obtained from 30.2 mg of sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonyl-5-methylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate.

NMR (CDCl 3 ) δ: 1.21 (9H, s), 1.27 (3H, t, J=7.1 Hz), 1.37 (3H, d, J=6.3 Hz), 2.68 (3H, s), 3.20 (3H, s), 3.34 (1H, dd, J 1 =6.6 Hz, J 2 =2.8 Hz), 3.45 (1H, m), 4.28 (1H, m), 4.36 (1H, dd, J 1 =9.9 Hz, J 2 =2.8 Hz), 5.86 (1H, d, J=5.5 Hz), 6.00 (1H, d, J=5.5 Hz), 8.29 (1H, s).

›Example 108

Sodium (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonylaminoacetylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonylaminoacetylimidazo-[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 106 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylaminoacetylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate was obtained from 159 mg of 4-nitrobenzyl (1R,3R,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-oxo-1-carbapenam-3-carboxylate and 264 mg of 7-methanesulfonylaminoacetyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 1.31 (3H, d, J=7.1 Hz), 1.40 (3H, d, J=6.3 Hz), 3.01 (3H, s), 3.40 (1H, dd, J 1 =6.5 Hz, J 2 =2.9 Hz), 3.52 (1H, m), 4.33 (1H, m), 4.43 (1H, dd, J 1 =9.7 Hz, J 2 =2.9 Hz), 4.69 (2H, d, J=5.2 Hz), 5.29 (1H, d, J=13.6 Hz), 5.38 (1H, br), 5.53 (1H, d, J=13.6 Hz), 7.68 (2H, d, J=8.8 Hz), 8.01 (1H, s), 8.25 (2H, d, J=8.8 Hz), 8.49 (1H, s).

b) Sodium (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonylaminoacetylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-b), 65.0 mg of the title compound was obtained from 106 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylaminoacetylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate.

NMR (D 2 O) δ (HOD=4.80 ppm): 1.24 (3H, d, J=6.9 Hz), 1.35 (3H, d, J=6.3 Hz), 3.19 (3H, s), 3.55 (2H, m), 4.32 (2H, m), 4.59 (2H, s), 7.96 (1H, s), 8.11 (1H, s).

›Example 109

Sodium (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-1-methyl-2-(5-methyl-7-methylimidazo[5,1-thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-b), 24.3 mg of the title compound was obtained from 42.9 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(5-methyl-7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate.

NMR (D 2 O) δ (HOD=4. 80 ppm): 1.24 (3H, d, J=6. 9 Hz), 1.33 (3H, d, J=5.9 Hz), 2.33 (3H, s), 2.49 (3H, s), 3.54 (2H, m), 4.29 (2H, m), 7.70 (1H, s).

›Example 110

Sodium (1S,5R,6S-6-((1R)-1-Hydroxyethyl)-2-[7-(methanesulfonylaminomethyl)imidazo[5,1-b]thiazol-2-yl]-1-methyl-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-[7-(methanesulfonylaminomethyl)-imidazo[5,1-b]thiazol-2-yl]-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 69.4 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-[7-(methanesulfonylaminomethyl)imidazo[5,1-b]thiazol-2-yl]-1-methyl-1-carbapen-2-em-3-carboxylate was obtained as an yellowish orange oil from 124 mg of 4-nitrobenzyl (1R,3R,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-oxo-1-carbapenam-3-carboxylate and 196 mg of 7-methanesulfonylaminomethyl-2-(tri-n-butylstannyl)-imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 1.30 (3H, d, J=7.3 Hz), 1.39 (3H, d, J=6.3 Hz), 2.91, 2.94 (total 3H, s each), 3.35-3.40 (2H, m), 4.25-4.45 (4H, m), 5.15 (1H, br·t), 5. 27 (1H, d, J=13.5 Hz), 5.52 (1H, d, J=13.5 Hz), 6.87 (1/5H, d, J=4.2 Hz), 7.40 (1/5H, d, J=4.2 Hz), 7.68 (2H, d, J=8.8 Hz), 7.98 (4/5H, s), 8.24 (2H, d, J=8.8 Hz), 8.32 (4/5H, s); MS (TSP): 576 (M + +H).

b): Sodium (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-[7-(methanesulfonylaminomethyl)imidazo[5,1-b]thiazol-2-yl]-1-methyl-1-carbapen-2-em-3-carboxylate

The title compound (18.2 mg) was obtained as a light yellow flocculate in the same manner as in Example 1-b), except that 68 mg 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-[7-(methanesulfonylaminomethyl)imidazo-[5,1-b]thiazol-2-yl]-1-methyl-1-carbapen-2-em-3-carboxylate was used as a starting compound and the purification was carried out by column chromatography on Cosmosil 40C18-PREP.

NMR (D 2 O) δ (HOD=4.80 ppm): 1.25 (3H, d, J=7.4 Hz), 1.32 (3H, d, J=6.3 Hz), 2.99 (3H, s) 3.49-3.62 (2H, m), 4.24-4.35 (2H, m), 4.34 (2H, s), 7.88 (1H, s), 8.09 (1H, s); MS (TSP): 485 (M + +2Na), 463 (M + Na), 441 (M + +H).

›Example 111

Sodium (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-1-methyl-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 14.0 g of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo-[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate was obtained from 111.7 g of 4-nitrobenzyl (1R,3R,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-oxo-1-carbapenam-3-carboxylate and 14.0 g of 7-methylthio-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 1.31 (3H, d, J=7.13 Hz), 1.40 (3H, d, J=6.3 Hz), 2.43 (3H, s), 3.35-3.40 (1H, s), 3.41-3.52 (1H, m), 4.30-4.42 (2H, m), 5.29 (1H, d, J=13.7 Hz), 5.53 (1H, d, J=13.7 Hz), 7.67 (2H, d, J=8.9 Hz), 8.02 (1H, s), 8.23 (2H, d, J=8.9 Hz), 8.29 (1H, s).

b) Sodium (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-1-methyl-2-7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

The title compound (511 mg) was obtained from 103 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo-[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate in the same manner as in Example 1-b); except that the purification was carried out using Cosmosil 40C18-PREP (10% aqueous methanol).

NMR (D 2 O) δ (HOD=4.80 ppm): 1.25 (3H, d, J=7.2 Hz), 1.32 (3H, d, J=6.4 Hz), 2.37 (3H, s), 3.50-3.60 (2H, m), 4.25-4.35 (2H, m), 7.90 (1H, s), 8.12 (1H, s).

›Example 112

Sodium (5R,6S)-2(7-Dimethylaminosulfonyimidazo[5,1-b]thiazol-2-yl)-6-((1R)-hydroxy-ethyl)-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (5R,6S)-2-(7-Dimethylaminosulfonylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 0.29 g of 4-nitrobenzyl (5R,6S)-2-(7-dimethylaminosulfonylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate was obtained from 0.35 g of 4-nitrobenzyl (3R,5R,6S)-6-((1R)-1-hydroxyethyl)-2-oxo-1-carbapenam-3-carboxylate and 0.52 g of 7-dimethylamino-sulfonyl-2-(tri-n-butylstannyl)imidazo[5,1-b]-thiazole.

NMR (DMSO-d 6 ) δ: 1.17 (3H, d, J=6.0 Hz), 2.67 (6H, s), 3.40-3.55 (3H, m), 3.95-4.05 (1H, m), 4.20-4.30 (1H, m), 5.18-5.18 (1H, d, J=4.9 Hz), 5.42 (1H, d, J=14.0 Hz), 5.57 (1H, d, J=14.0 Hz), 7.75 (2H, d, J=8.5 Hz), 8.24 (2H, d, J=8.5 Hz), 8.42 (1H, s), 8.23 (1H, s).

b) Sodium (5R,6S)-2-(7-Dimethylaminosulfonylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

The title compound (84 mg) was obtained from 150 mg of 4-nitrobenzyl (5R,6S)-2-(7-dimethylaminosulfonylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate in the same manner as in Example 1-b), except that the purification was carried out using Cosmosil 40C18-PREP (5% aqueous methanol).

NMR (D 2 O) δ (HOD=4.801 ppm): 1.32 (3H, d, J=6.2 Hz), 3.30-3.40 (2H, s), 3.50-3.55 (1H, m), 4.25-4.35 (2H, m), 7.90 (1H, s), 8.23 (1H, s).

›Example 113

Sodium (5R,6S)-2-(7-Aminosulfonylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (5R,6S)-2-(7-t-Butyldimethylsilylaminosulfonylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 0.36 g of 4-nitrobenzyl (5R,6S)-2-(7-t-butyldimethylsilylaminosulfonylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate was obtained from 0.28 g of 4-nitrobenzyl (3R,5R,6S)-6-((1R)-1-hydroxyethyl)-2-oxo-1-carbapenam-3-carboxylate and 0.44 9 of 7-t-butyldimethylsilylaminosulfonyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (DMSO-d 6 ) δ: 0.11 (6H, s), 0.86 (9H, s), 1.17 (3H, d, J=6.0 Hz), 3.40-3.55 (3H, m), 3.95-4.05 (1H, m), 4.20-4.30 (1H, m), 5.42 (1H, d, J=14.0 Hz), 5.57 (1H, d, J=14.0 Hz), 7.65 (1H, s), 7.76 (2H, d, J=8.5 Hz), 8.23 (2H, d, J=8.5 Hz), 8.35 (1H, s), 8.42 (1H, s).

b) Sodium (5R,6S)-2-(7-Aminosulfonylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3carboxylate

In the same manner as in Example 99-b), 29 mg of the title compound was obtained from 83 mg of 4-nitrobenzyl (5R,6S)-2-(7-t-butyldimethylsilylaminosulfonylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate.

NMR (D 2 O) δ (HOD=4.80 ppm): 1.32 (3H, d, J=6.3 Hz), 3.25-3.40 (2H, m), 3.50-3.55 (1H, m), 4.20-4.35 (2H, m), 7.84 (1H, s), 8.19 (1H, s).

›Example 114

Sodium (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-1-methyl-2-[7-((E)-3-oxo-1-buten-1-yl)imidazo[5,1-b]thiazol-2-yl]-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-[7-((E)-3-oxo-1-buten-1-yl)imidazo[5,1-b]thiazol-2-yl]-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 89 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-[7-((E)-3-oxo-1-buten-1-yl)imidazo[5,1-b]-thiazol-2-yl]-1-carbapen-2-em-3-carboxylate was obtained from 320 mg of 4-nitrobenzyl (1R,3R,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-oxo-1-carbapenam-3-carboxylate and 208 mg of 7-((E)-3-oxo-1-buten-1-yl)-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 1.33 (3H, d, J=7.3 Hz), 1.41 (3H, d, J=6.4 Hz), 2.38 (3H, s), 3.38 (1H, dd, J=6.4 Hz, J 2 =2.7 Hz), 3.50 (1H, m), 4.33 (1H, m), 4.41 (1H, dd, J 1 =9.6 Hz, J 2 =2.7 Hz), 5.29, (1H, d, J=13.6 Hz), 5.53 (1H, d, J=13.6 Hz), 6.42 (1H, d, J=16.1 Hz), 7.63 (1H, d, J=16.1 Hz), 7.69 (2H, d, J=9.0 Hz), 8.09 (1H, s), 8.25 (2H, d, J=9.0 Hz), 8.39 (1H, s).

b) Sodium (1S,5R,6S)-6-((R)-1-Hydroxyethyl)-1-methyl-2-[7-((E)-3-oxo-1-buten-1-yl)imidazo[5,1-b]thiazol-2-yl]-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-b), 37 mg of the title compound was obtained from 85 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-[7-((E)-3-oxo-1-buten-1-yl)imidazo[5,1-b]thiazol-2-yl]-1-carbapen-2-em-3-carboxylate.

NMR (D 2 O) δ (HOD=4.80 ppm): 1.08 (3H, d, J=7.0 Hz), 1.20 (3H, d, J=6.4 Hz), 2.21 (3H, s), 3.35 (1H, dd, J 1 =6.4 Hz, J 2 =2.7 Hz), 3.42 (1H, m), 4.15 (1H, m), 4.17 (1H, dd, J 1 =8.6 Hz, J 2 =2.2 Hz), 5.87 (1H, d, J=15.8 Hz), 7.32 (1H, d, J=15.8 Hz), 7.74 (1H, s), 7.96 (1H, s).

›Example 115

Sodium (1S,5R,6S)-2-(7-formyl-5-Methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (1S,5R,6S)-2-[7-(t-butyldimethylsilyloxy)methyl-5-methylimidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 313 mg of 4-nitrobenzyl (1S,5R,6S)-2-[7-(t-butyldimethylsilyloxy)methyl-5-methylimidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate was obtained from 730 mg of 4-nitrobenzyl (1R,3R,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-oxo-1-carbapenam-3-carboxylate and 1.2 g of 7-(t-butyldimethylsilyloxy)methyl-5-methyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 0.13 (6H, sx2), 0.96 (9H, s), 1.31 (3H, d, J=7.3 Hz), 1.39 (3H, d, J=6.3 Hz), 2.55 (3H, s), 3.35 (1H, dd, J 1 =6.6 Hz, J 2 =2.7 Hz), 3.45 (1H, m), 4.30 (1H, m), 4.35 (1H, dd, J 1 =9.5 Hz, J 2 =2.7 Hz), 4.81 (2H, s), 5.26 (1H, d, J=13.6 Hz), 5.53 (1H, J=13.6 Hz), 7.67 (2H, d, J=8.7 Hz), 8.18 (1H, s), 8.23 (2H, d, J=8.7 Hz).

b) 4-Nitrobenzyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-hyroxymethyl-5-methylimidazo-5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

Acetic acid (0.28 ml)-and 1.6 ml of a 1 M tetrabutylammonium fluoride/THF solution were added to 313 mg of 4-nitrobenzyl (1S,5R,6S)-2-[7-(t-butyldimethylsilyloxy)methyl-5-methylimidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate. The mixture was stirred at room temperature for 3.5 hr. The reaction solution was adjusted to pH 7 by the addition of a saturated aqueous sodium hydrogencarbonate solution. The reaction solution was then extracted with ethyl acetate, washed with saturated brine, and dried over magnesium sulfate. The reaction solution was then concentrated under the reduced pressure. The residue was purified by column chromatography to give 279 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-hydroxymethyl-5-methylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate.

NMR (CDCl 3 ) δ: 1.28 (3H, d, J=7.3 Hz), 1.37 (3H, d, J=6.3 Hz), 2.56 (3H, s), 3.33 (1H, dd, J 1 =6.3 Hz, J 2 =2.7 Hz), 3.44 (1H, s), 4.23 (1H, m), 4.32 (1H, dd, J 1 =9.5 Hz, J 2 =2.7 Hz), 4.64 (2H, s), 5.28 (1H, d, J=13.8 Hz), 5.52 (1H, d, J=13.7 Hz), 7.67 (2H, d, J=9.0 Hz), 8.15 (1H, s), 8.23 (2H, d, J=9.0 Hz).

c) 4-Nitrobenzyl (1S,5R,6S)-2-(7-Formyl-5-methylimidazo[5,1-b]thiazol-2-yl)-6-(1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

4-Nitrobenzyl (1S,5R,6S)-6((1R)-1-Hydroxyethyl)-2-(7-hydroxymethyl-5-methylimidazo-[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (279 mg) was dissolved in 30 ml of dichloromethane. Manganese dioxide (500 mg) was added to the solution. The mixture was stirred at room temperature for 14 hr. The reaction solution was filtered. The filtrate was concentrated under the reduced pressure. The residue was purified by column chromatography on silica gel to give 89 mg of 4-nitrobenzyl (1S,5R,6S)-2-(7-formyl-5-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate.

NMR (CDCl 3 ) δ: 1.32 (3H; d, J=71.3 Hz), 1.40 (3H, d, J=6.3 Hz), 2.67 (3H, s), 3.38 (1H, dd, J 1 =6.3 Hz, J 2 =2.9 Hz), 3.52 (1H, s), 4.33 (1H, m), 4.42 (1H, dd, J 1 =9.7 Hz, J 2 =2.9 Hz), 5.27 (1H, d, J=13.6 Hz), 5.55 (1H, d, J=13.6 Hz), 7.68 (2H, d, J=9.0 Hz), 8.25 (2H, d, J=9.0 Hz), 8.37 (1H, s), 9.85 (1H, s).

d) Sodium (1S,5R,6S)-2-(7-formyl-5-Methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl-1-methyl-1-carbapen-2-elm-3-carboxylate

In the same manner as in Example 1-b), 29 mg of the title compound was obtained from 89 mg of 4-nitrobenzyl (1S,5R,6S)-2-(7-formyl-5-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-3-carboxylate.

NMR (D 2 O)δ (HOD=4.80 ppm): 1.09 (3H, d, J=7.1 Hz), 1.20 (3H, d, J=6.3 Hz), 2.43 (3H, s), 3.37 (1H, dd, J 1 =6.3 Hz, J 2 =2.7 Hz), 3.49 (1H, m), 4.14 (1H, q, J=6.3 Hz), 4.20 (1H, dd, J 1 =9.3 Hz, J 2 =2.7 Hz), 7.75 (1H, s), 9.25 (1H, s).

›Example 116

Sodium (5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 1.79 g of 4-nitrobenzyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate was obtained from 2.30 g of 4-nitrobenzyl (3R,5R,6S)-6-((1R)-1-hydroxyethyl)-2-oxo-1-carbapenam-3-carboxylate and 3.48 g of 7-methylthio-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 1.40 (3H, d, J=6.3 Hz), 2.42 (3H, s), 3.32 (3H, m), 4.32 (2H, m), 5.32 (1H, d, J=13.2 Hz), 5.55 (1H, d, J=13.2 Hz), 7.69 (2H, d, J=9.1 Hz), 8.01 (1H, s), 8.18 (1H, s), 8.25 (2H, d, J=9.1 Hz).

b) Sodium (5R,6S)-6-(Hydroxyethyl)-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-b), 54 mg of the title compound was obtained from 98 mg of 4-nitrobenzyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate.

NMR (D 2 O) δ (HOD=4.65 ppm): 1.19 (3H, d, J=6.3 Hz), 2.24 (3H, s), 3.16 (2H, m), 3.3 (1H,dd, J 1 6.0 Hz, J 2 2.9 Hz), 4.14 (2H, m), 7.60 (1H s), 7.98 (1H, s).

›Example 117

Sodium (5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfinylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

a) 4-Nitrobenzyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfinylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

A reaction was carried out in the same manner as in Example 44-b), except that 639 mg of 4-nitrobenzyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate and 1.57 g of oxone were used as the starting compounds. The reaction product was purified by column chromatography on silica gel (dichloromethane:methanol=20:1 to 10:1) to give 267 mg of 4-nitrobenzyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfinylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers).

NMR (CDCl 3 ) δ: 1.40 (3H, d, J=6.1 Hz), 2.95, 2.95 (total 3H, s each), 3.33 (3H, m), 4.32 (2H, m), 5.31 (1H, d, J=13.6 Hz), 5.53 (1H, d, J=13.6 Hz), 7.68 (2H, d, J=8.8 Hz), 8.06 (1H, s), 8.24 (2H, d, J=8.8 Hz), 8.38 (1H, s).

b) Sodium (5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfinylimidazo[5,1-b]thiazol2y)-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example 1-b), 16 mg of the title compound was obtained from 74 mg of 4-nitrobenzyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfinylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers).

NMR (DMSO-d 6 ) δ: 1.15 (3H, d, J=6.4 Hz), 2.83 (3H, s), 3.12 (2H, m), 3.21 (1H, m), 3.91 (1H, m), 4.01 (1H, m), 5.05 (1H, s), 7.95 (1H, s), 8.23 (1H, s).

›Example 118

Sodium (5R,6S)-2-[7-(N,N-Dimethylaminosulfonylamino)acetylimidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (5R,6S)-2-[7-(N,N-Dimethylaminosulfonylamino)acetylimidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 162 mg of 4-nitrobenzyl (5R,6S)-2-[7-(N,N-dimethylaminosulfonylamino)acetylimidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate was obtained from 244 mg of 4-nitrobenzyl (3R,5R,6S)-6-((1R)-1-hydroxyethyl)-2-oxo-1-carbapenam-3-carboxylate and 222 mg of 7-(N,N-dimethylaminosulfonylamino)acetyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (DMSO-d 6 ) δ: 1.18 (3H, d, J=6.1 Hz), 2.67 (6H, s), 3.4-3.6 (3H, m), 4.0-4.1 (1H, m), 4.2-4.35 (1H, m), 4.43 (2H, s), 5.44 (1H, d, J=13.7 Hz), 5.58 (1H, d, J=13.7 Hz), 7.77 (2H, d, J=8.5 Hz), 8.25 (2H, d, J=8.5 Hz), 8.37 (1H, s), 8.51 (1H, s).

b) Sodium (5g,6S)-2-[7-(N,N-Dimethylaminosulfonylamino)acetylimidazo[5,1-b]thiazol-2-yl]-6-(1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

The title compound (49.5 mg) was obtained from 160 mg of 4-nitrobenzyl (5R,6S)-2-[7-(N,N-dimethylaminosulfonylamino)acetylimidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate in the same manner as in Example 1-b), except that, the purification was carried out by column chromatography on Cosmosil 40C18PREP (10% aqueous methanol).

NMR (D 2 O) δ ((HOD=4.80 ppm): 1.33 (3H, d, J=6.3 Hz), 2.83 (6H, s), 3.2-3.4 (2H, m), 3.52 (1H, dd, J 1 =5.7 Hz, J 2 =2.3 Hz), 4.2-4.35 (2H, m), 4.4-4.6 (2H, m), 7.81 (1H, s), 8.06 (1H, s).

›Example 119

Sodium (1S,5R,6S)-2-[7-(N,N-Dimethylaminosulfonylamino)acetylimidazo[5,1-1-b]thiazol-2-yl]-6-(1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (1S,5R,6S)-2-[7-(N,N-dimethylaminosulfonylamino)acetylimidazo[5,1-b]thiazol-2-yl]-6-(1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 65.0 mg of 4-nitrobenzyl (1S,5R,6S)-2-[7-(N,N-dimethylaminosulfonylamino)acetylimidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate was obtained from 127 mg of 4-nitrobenzyl (1R,3R,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-oxo-1-carbapenam-3-carboxylate and 222 mg of 7-(N,N-dimethylaminosulfonylamino)acetyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 1.31 (3H, d, J=71.1 Hz), 1.40 (3H, d, J=6.3 Hz), 2.83 (6H, s), 3.39 (1H, dd, J 1 =6.6 Hz, J 2 =2.7 Hz), 3.45-3.6 (1H, m), 4.3-4.4 (1H, m), 4.43 (1H, dd, J 1 =9.5 Hz, J 2 =2.7 Hz), 4.57 (2H, d, J=5.0 Hz), 5.28 (1H, d, J=13.5 Hz), 5.42 (1H, bs·s), 5.53 (1H, d, J=13.5 Hz), 7.68 (2H, d, J=8.5 Hz), 8.01 (1H, s), 8.24 (2H, d, J=8.5 Hz), 8.48 (1H, s).

b) Sodium (1S,5R,6S)-2-[7-(N,N-Dimethylaminosulfonylamino)acetylimidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

The title compound (34.4 mg) was obtained from 65.0 mg of 4-nitrobenzyl (i1S,5R,6S)-2-[7-(N,N-dimethylaminosulfonylamino)acetylimidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate in same manner as in Example 1-b), except that the purification was carried out by column chromatography on Cosmosil 40C18-PREP (10% aqueous methanol).

NMR (D 2 O) δ (HOD=4.80 ppm): 1.22 (3H, d, J=6.9 Hz), 1.33 (3H:, d, J=6.3 Hz), 2.83 (6H, s), 3.45-3.6 (2H, m), 4.2-4.351 (2H, m), 4.43 (1H, d, J=18.5 Hz), 4.54 (1H, d, J=18.5 Hz), 7.90 (1H, s), 8.06 (1H, s).

›Example 120

Sodium (5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(5-methyl-7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-b), 43 mg of the title compound was obtained from 72 mg of 4-nitrobenzyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(5-methyl-7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate.

NMR (D 2 O) δ (HOD=4.65 ppm): 1.18 (3H, d, J=5.9 Hz), 2.20 (3H, s), 2.36 (3H, s), 3.12 (2H, m), 3.37 (1H, m), 4.13 (21, m), 7.44 (1H, s).

›Example 121

Sodium (1S,5R,6S)-2-(7-Aminoacetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-[7-(4-nitrobenzyloxycarbonylamino)acetylimidazo[5,1-b]thiazol-2-yl]-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 468 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-[7-(4-nitrobenzyloxy-carbonylamino)acetylimidazo[5,1-b]thiazol-2-yl]-1-carbapen-2-em-3-carboxylate was obtained from 362 mg of 4-nitrobenzyl (1R,3R,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-oxo-1-carbapenam-3-carboxylate and 714 mg of 7-(4-nitrobenzyloxycarbonylamino)acetyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (DMSO-d 6 ) δ: 1.21 (3H, d), 1.24 (3H, d), 3.42 (1H, dd), 3.74 (1H, m), 4.06 (1H, m), 4.36 (1H, dd), 4.47, (2H, d), 5.16(1H, d), 5.21 (2H, s), 5.48 (1H, d), 5.54 (1H, d), 7.65 (2H, d), 7.75 (2H, d), 8.21 (2H, d), 8.26 (2H, d), 8.34 (1H, s), 8.60 (1H, s).

b) Sodium (1S,5R,6S)-2-(7-Aminoacetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

The title compound (25 mg) was obtained from 140 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-[7-(4-nitrobenzyloxycarbonylamino)acetylimidazo[5,1-b]thiazol-2-yl]-1-carbapen-2-em-3-carboxylate in the same manner as in Example 1-b) except that the purification was carried out by column chromatography on Cosmosil 40C18-PREP (20% aqueous methanol).

NMR (D 2 O) δ (HOD 4.80 ppm): 1.21 (3H, d), 1.33 (3H, d), 3.50 (2H, m), 4.30 (2H, m), 4.42 (2H, ABq), 7.91 (1H, s), 8.12 (1H, s).

›Example 122

Sodium (1S,5R,65)-2-(7-Aminomethylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-methyl-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-[7-(4-nitrobenzyloxycarbonylaminomethyl)imidazo[5,1-b]thiazol-2-yl]-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 228 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-[7-(4-nitrobenzyloxycarbonylaminomethyl)imidazo[5,1-b]thiazol-2-yl]-1-carbapen-2-em-3-carboxylate was obtained from 181 mg of 4-nitrobenzyl (1R,3R,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2oxo-1-carbapenam-3-carboxylate and 373 mg of 7-(4-nitrobenzyloxycarbonylamino)methyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (DMSO-d 6 ) δ: 1.20 (6H, d), 3.39 (1H, dd), 3.62 (1H, m), 4.05 (1H, m), 4.24 (2H, d), 4.32, (1H, dd), 5.12 (1H, d), 5.20 (2H, s), 5.34 (1H, d), 5.48 (1H, d), 7.61 (2H, d), 7.71 (2H, d), 8.00 (1H, m), 8.12 (1H, s), 8.18 (4H, d), 8.35 (1H, s).

b) Sodium (1S,5R,6S)-2-(7-Aminomethylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

The title compound (24 mg) was obtained from 81 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R) 1-hydroxyethyl)-1-methyl-2-[7-(4-nitrobenzyloxycarbonylaminomethyl)imidazo[5,1-b]thiazol-2-yl]-1-carbapen-2-em-3-carboxylate in the same manner as in Example 1-b), except that the purification was carried out by column chromatography on Cosmosil 40C18-PREP (30% aqueous methanol).

NMR (D 2 O) δ (HOD 4.80 ppm): 1.20 (3H, d), 1.31 (3H, d), 3.49 (2H, m), 4.13 (1H, dd), 4.22 (2H, s), 4.27 (1H, m), 7.85 (1H, s), 8.13 (1H, s).

›Example 123

Sodium (1S,5R,6S)-2-[7-(2-Aminoethanesulfonylamino)acetylimidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-1-methyl-2-[7-[2-(4-nitrobenzyloxycarbonyl)aminoethanesulfonylamino]acetylimidazo[5,1-b]thiazol-2-yl-]1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 57.2 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-[7-[2-(4-nitrobenzyloxycarbonyl)aminoethanesulfonylamino]acetylimidazo[5,1-b]thiazol-2-yl]-1-carbapen-2-em-3-carboxylate was obtained from 120 mg of 4-nitrobenzyl (1R,3R,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-oxo-1-carbapenram-3-carboxylate and 192 mg of 7-[2-(4-nitrobenzyloxycarbonyl)aminoethane-sulfonylamino]acetyl-2-(tri-n-butylstannyl)-imidazo[5,1-b]thiazole.

NMR (DMSO-d 6 ) δ: 1.19 (3H, d, J=6.5 Hz), 1.22 (3H, d, J=7.3 Hz), 3.2-3.3 (2H, m), 3.4 3.5 (3H, m), 3.7-3.8 (1H, m), 4.0-4.1 (1H, m), 4.3-4.4 (1H, m), 4.49 (2H, s), 5.17 (2H, s), 5.39 (1H, d, J=14.3 Hz), 5.53 (1H, d, J=14.3 Hz), 7.58 (2H, d, J=8.6 Hz), 7.74 (2H, d, J=8.6 Hz), 8.18 (2H, d, J=8.6 Hz), 8.21 (2H, d, J=8.6 Hz), 8.36 (1H, s), 8.59 (1H, s).

b) Sodium (1S,5R,6S)-2-[7-(2-Aminoethanesulfonylamino)acetylimidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

The title compound (20.1 mg) was obtained from 55.4 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-[7-[2-(4-nitrobenzyloxycarbonyl)aminoethanesulfonylamino]acetylimidazo[5,1-b]thiazol-2-yl]-1-carbapen-2-em-3-carboxylate in the same manner as in Example 1-b), except that the purification was carried out by column chromatography on Cosmosil 40C18-PREP (10% aqueous methanol).

NMR (D 2 O) δ (HOD=4.80 ppm): 1.20 (3H, d, J=7.1 Hz), 1.33 (3H, d, J=6.4 Hz), 3.4-3.55 (4H, m), 3.55-3.7 (2H, m), 4.2-4.35 (2H, m), 4.78 (2H, s), 7.83 (1H, s), 7.99 (1H, s).

›Example 124

Sodium (5R,6S)-2-[7-(2-Aminoethanesulfonylamino)acetylimidazo[5,1-b]thiazol-2-yl]-6-((1R)-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (5R,6S)-6-((1R)-1-Hydroxyethyl)-2-[7-[2-(4-nitrobenzyloxycarbonyl)-aminoethanesulfonylamino]acetylimidazo[5.1-b]thiazol-2-yl]-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 80.6 mg of 4-nitrobenzyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-[7-[2-(4-nitrobenzyloxycarbonyl)aminoethaneisulfonyliamino]acetylimidazo[5,1-b]thiazol-2-yl]-1-carbapen-2-em-3-carboxylate was obtained from 99 mg of 4-nitrobenzyl (3R,5R,6S)-6-((1R)-1-hydroxyethyl)-2-oxo-1-carbapenam-3-carboxylate and 215 mg of 7-[2-(4-nitrobenzyloxycarbonyl)aminoethanesulfonylamino]-acetyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 1.41 (3H, d, J=6.3 Hz), 3.25-3.4 (5H, m), 3.7-3.8 (2H, m), 4.3-4.45 (2H, m) 4.68 (2H, d, J=5.0 Hz), 5.19 (2H, s), 5.33 (1H, d, J=13.3 Hz), 5.55 (1H, d, J=13.3 Hz), 7.49 (2H, d, J=8.8 Hz), 7.70 (2H, d, J=8.8 Hz), 7.99 (1H, s), 8.17 (2H, d, J=8.8 Hz), 8.25 (2H, d, J=8.8 Hz), 8.33 (1H, s).

b) Sodium (5R,6S)-2-[7-(2-Aminoethanesulfonylamino)acetylimidazo[5,1-b]thiazol-2-yl]6-(( R)-1-hydroxyethyl)l-carbapen-2-em-3-carboxylate

The title compound (21.4 mg) was obtained from 80.6 mg of 4-nitrobenzyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-[7-[2-(4-nitrobenzyloxycarbonyl)-aminoethanesulfonylamino]acetylimidazo[5,1-b]thiazol-2-yl]-1-carbapen-2-em-3-carboxylate in the same manner as in Example 1-b), except that the purification was carried out by column chromatography on Cosmosil 40C18-PREP (20% aqueous methanol).

NMR (D 2 O) δ (HOD=4.80ppm): 1.33 (3H, d, J=6.6 Hz), 3.0-3.25 (2H, m), 3.5-3.75 (5H, m), 4.2-4.35 (2H, m), 4.51 (2H, s), 7.59 (1H, s), 7.94 (1H, s).

›Example 125

Sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(5-methanesulfonylimidazo-[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-1-methyl-2-(5-methylthioimidazo-[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 643 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(5-methylthioimidazo-[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate was obtained from 847 mg of 4-nitrobenzyl (1R,3R,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-oxo-1-carbapenam-3carboxylate and 1.13 g of 5-methylthio-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 1.32 (3H, d, J=7.3 Hz), 1.39 (3H, d, J=6.3 Hz), 2.55 (3H, s), 3.36 (1H, m), 3.49 (1H, m), 4.31 (1H, m), 4.36, (1H, dd, J 1 =9.5 Hz, J 2 =2.7 Hz), 5.28 (1H, d, J=13.6 Hz), 5.53 (1H, d, J=13.6 Hz), 7.11 (1H, s), 7.67 (2H, d, J=8.7 Hz), 8.18 (1H, s), 8.23 (2H, d, J=8.7 Hz).

b) 4-Nitrobenzyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(5-methanesulfonylimidazo[5,1-b]thiazol-9-yl-1-methyl-1-carbapen-2-em-3-carboxylate

A reaction was carried in the same manner as in Example 44-b), except that 112 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(5-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate and 268 mg of oxone were used as the starting compounds. The reaction product was purified by column chromatography on silica gel (dichloromethane:methanol=20:1 to 10:1) to give 75 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(5-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate.

NMR (CDCl 3 ) δ: 1.34 (3H, d, J=7.3 Hz), 1.39 (3H, d, J=6.3 Hz), 3.33 (3H, s), 3.38 (1H, m), 3.59 (1H, m), 4.31 (1H, m), 4.38, (1H, dd, J 1 9.6 Hz, J 2 =2.8 Hz), 5.30 (1H, d, J=13.7 Hz), 5.53 (1H, d, J=13.7 Hz), 7.29 (1H, s), 7.66 (2H, d, J=8.8 Hz), 8.23 (2H, d, 8.8 Hz), 8.54 (1H, s).

c) Sodium (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(5-methanesulfonylimidazo[5,1-b]thiazol 2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-b), 32 mg of the title compound was obtained from 75 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(5-methanesulfonylimidazo[5,1-b]thiazol2yl)-1-methyl-1-carbapen-2-em-3-carboxylate.

NMR (D 2 O) δ (HOD=4.65 ppm): 1.11 (3H, d, J=7.3 Hz), 1.18 (3H, d, J=6.5 Hz), 3.23 (3H, s), 3.40, (1H, dd, J 1 =6.1 Hz, J 2 =2.6 Hz), 3.50 (1H, m), 4.13 (1H, m), 4.19, (1H, dd, J 1 =9.3 Hz, J 2 =2.5 Hz), (1H, s), 8.02 (1H, s).

›Example 126

Sodium (1S,5R,6S)-6-(((1R)-1-Hydroxyethyl)-1-methyl-2-(5-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-b), the title compound (44 mg) was obtained from 107 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(5-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate.

NMR (D 2 O) δ (HOD=4.65 ppm): 1.12 (3H, d, J=7.1 Hz), 1.19 (3H, d, J=6.6 Hz), 2.32 (3H, s), 3.38, (1H, dd, J 1 =5.4 Hz, J 2 =2.1 Hz), 3.46 (1H, m), 4.15 (2H, m), 6.89 (1H, s), 7.01 (1H, s).

›Example 127

Sodium (1S,5R,6S)-2-[5,7-bis(Methylthio)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (1S,5R,6S)-2-[5,7-bis(Methylthio)imidazo[5.1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 720 mg of 4-nitrobenzyl (1S,5R,6S)-2-[5,7-bis(methylthio)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate was obtained from 762 mg of 4-nitrobenzyl (1R,3R,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-oxo-1-carbapenam-3-carboxylate and 1.10 g of 5,7-bis(methylthio)-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 1.31. (3H, d, J=7.3 Hz), 1.39 (3H, d, J=6.3 Hz), 2.43 (3H, s), 2.58 (3H, s), 3.36 (1H, m), 3.49 (1H, m), 4.33 (2H, m), 5.28 (1H, d, J=13.7 Hz), 5.53 (1H, d, J=13.4 Hz), 7.67 (2H, d, J=9.0 Hz), 8.13 (1H, s), 8.23 (2H, d, J=9.0 Hz).

b) Sodium (1S,5R,6S)-2-[5,7-bis(Methylthio)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-b), 42 mg of the title compound was obtained from 89 mg of 4-nitrobenzyl (1S,5R,6S)-2-[5,7-bis(methylthio)-imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxy-ethyl)-1-methyl-1-carbapen-2-em-3-carboxylate.

NMR (D 2 O) δ (HOD=4.65 ppm): 1.09 (3H, d, J=7.3 Hz), 1.18 (3H, d, J=6.3 Hz), 2.20 (3H, s), 2.34 (3H, s), 3.36, (1H, dd, J 1 =6.0 Hz, J 2 =2.6 Hz), 3.45 (1H, m), 4.15 (2H, m), 7.66 (1H, s).

›Example 128

Sodium (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-1-methyl-2-(7-phenylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-1-methyl-2-(7-phenylthioimidazo-[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 92.5 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-phenylthioimidazo-[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate was obtained from 146 mg of 4-nitrobenzyl (1R,3R,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-oxo-1-carbapenam-3-carboxylate and 231 mg of 7-phenylthio-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 1.30 (3H, d, J=7.3 Hz), 1.39 (3H, d, J=6.2 Hz), 3.36 (1H, dd, J 1 =6.5 Hz, J 2 =2.8 Hz), 3.4-3.5 (1H, m), 4.25-4.35 (1H, m), 4.36 (1H, dd, J 1 =9.7 Hz, J 2 =2.8 Hz), 5.27 (1H, d, J=13.5 Hz), 5.52 (1H, d, J=13.5 Hz), 7.1-7.25 (5H, m), 7.67 (2H, d, J=8.7 Hz), 8.10 (1H, s), 8.24 (2H, d, J=8.7 Hz), 8.35 (1H, s).

b) Sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-phenylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

The title compound (23.9 mg) was obtained from 42.8 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-phenylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate in the same manner as in Example 1-b), except that the purification was carried out by column chromatography on Cosmosil 40C18-PREP (20% aqueous methanol).

NMR (D 2 O) δ (HOD=4.80 ppm): 1.17 (3H, d, J=6.9 Hz), 1.31 (3H, d, J=6.3 Hz), 3.35-3.5 (2H, m), 4.2-4.3 (2H, m), 7.1-7.3 (5H, m), 7.87 (1H, s), 8.15 (1H, s).

›Example 129

Sodium (5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methylthioimidazo[5,1-b]thiazol-3-yl)-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methylthioimidazo[5,1-b]-thiazol-3-yl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 230 mg of 4-nitrobenzyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methylthioimidazo[5,1-b]thiazol-3-yl)-1-carbapen-2-em-3-carboxylate was obtained from 348 mg of 4-nitrobenzyl (3R,5R,6S)-6-((1R)-1-hydroxyethyl)-2-oxo-1-carbapenam-3-carboxylate and 535 mg of 7-methylthio-3-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (DMSO-d 6 ) δ: 1.18 (3H, d), 2.31 (3H, s), 3.27 (1H, m) 3.56 (2H, m), 4.02 (1H, m), 4.42 (1H, m), 5.27 (1H, d), 5.31 (2H, ABq), 7.43 (1H, s), 7.50 (2H, d), 8.16 (2H, d), 8.30 (1H, s).

b) Sodium (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methylthioimidazo[5,1-b]thiazol-3-yl)-1-carbapen-2-em-3-carboxylate

The title compound (28 mg),was obtained from 100 mg of 4-nitrobenzyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methylthioimidazo[5,1-b]thiazol-3-yl)-1-carbapen-2-em-3-carboxylate in the same manner as in Example 1-b), except that the purification was carried out by column chromatography on Cosmosil 40C18-PREP (10-20% aqueous methanol).

NMR (D 2 O) δ (HOD 4.80 ppm): 1.21 (3H, d), 2.37 (3H, s), 3.18 (1H, dd), 3.44 (1H, dd), 3.58 (1H, dd), 4.28 (1H, m), 4.87 (1H, m), 7.08 (1H, s), 7.92 (1H, s).

›Example 130

Sodium (5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-phenylthioimidazo[5.1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-phenylthioimidazo[5,1-b]-thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 105.3 mg of 4-nitrobenzyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-phenylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate was obtained from 140 mg of 4-nitrobenzyl (3R,5R,6S)-6-((1R)-1-hydroxyethyl)-2-oxo-1-carbapenam-3-carboxylate and 232 mg of 7phenylthio-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (DMSO-d 6 ) δ: 1.17 (3H, d, J=6.2 Hz), 3.35-3.55 (3H, m), 3.95-4.05 (1H, m), 4.2-4.3 (1H, m), 5.39 (1H, d, J=13.8 Hz), 5.51 (1H, d, J=13.8 Hz), 7.0-7.3 (5H, m), 7.74 (2H, d, J=8.7 Hz), 8.22 (2H, d, J=8.7 Hz), 8.40 (1H, s), 8.43 (1H, s).

b) Sodium (5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-phenylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

The title compound (21.9 mg) was obtained from 47.1 mg of 4-nitrobenzyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-phenylthioimidazo[5,1-b]-thiazol-2-yl)-1-carbapen-2-em-3-carboxylate in the same manner as in Example 1-b), except that the purification was carried out by column chromatography on ° Cosmosil 40C18 PREP (10% aqueous methanol).

NMR (D 2 O) δ (HOD=4.80 ppm): 1.31 (3H, d, J=6.3 Hz), 3.05-3.25 (2H, m), 3.47 (1H;, dd, J 1 =5.8 Hz, J 2 =2.8 Hz), 4.2-4.3 (2H, m), 7.1-7.3 (5H, m), 7.62 (1H, s), 8.08 (1H,

›Example 131

Sodium (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-1-methyl-2-(3-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-1-methyl-2-(3-methylthioimidazo-[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 287 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(3-methylthioimidazo-[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate was obtained from 56 g of 4-nitrobenzyl (1R,3R,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-oxo-1-carbapenam-3-carboxylate and 2.05g of 3-methylthio-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 1.21 (3H, d, J=7.3 Hz), 1.38 (3H, d, J=6.3 Hz), 2.27 (3H, s), 3.38 (1H, m), 3.46 (1H, m), 4.43 (1H, m), 4.47, (1H, dd, J 1 =10.5 Hz, J 2 =3.1 Hz), 5.19 (1H, d, J=13.7 Hz), 5.39 (1H, d, J=13.7 Hz), 7.14 (1H, s), 7.50 (2H, d, J=9.0 Hz), 8.05 (1H, s), 8.14 (2H, d, J=9.0 Hz).

b) Sodium (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-1-methyl-2-(3-methylthioimidazo-[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-b), 37 mg of the title compound was obtained from 83 mg of 4-nitrobenzyl 1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(3-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate.

NMR (D 2 O) δ (HOD=4.65 ppm): 1.02 (3H, d, J=7.3 Hz), 1.15 (3H, d, J=6.3 Hz), 2.21 (3H, s), 3.31, (1H, m), 3.40 (1H, m), 4.13 (1H, m), 4.22 (1H, dd, J 1 =10.0 Hz, J 2 =3.0 Hz), 6.96 (1H, s), 8.15 (1H, s).

›Example 132

Sodium (1S,5R,6S)-2-(7-Ethylthioimidazo-[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (1S,5R,6S)-2-(7-Ethylthioimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 731 mg of 4-nitrobenzyl (1S,5R,6S)-2-(7-ethylthioimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate was obtained from 724 mg of 4-nitrobenzyl (1R,3R,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-oxo-1-carbapenam-3-carboxylate and 1.04 g of 7-ethylthio-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 1.26 (3H, t, J=7.3 Hz), 1.31 (3H, d, J=7.2 Hz), 1.40 (3H, d, J=6.1 Hz), 2.84 (2H, q, J=7.3 Hz), 3.37 (1H, dd, J 1 =6.5 Hz, J 2 =2.8 Hz), 3.4-3.5 (1H, m), 4.25-4.35 (1H, m), 4.38 (1H, dd, J 1 =9.4 Hz, J 2 =2.8 Hz), 5.28 (1H, d, J=13.7 Hz), 5.53 (1H, d, J=13.7 Hz), 7.68 (2H, d, J=8.4 Hz), 8.03 (1H, s), 8.24 (2H, d, J=8.4 Hz), 8.30 (1H, s).

b) Sodium (1S,5R,6S)-2-(7-Ethylthioimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

The title compound (87.5 mg) was obtained from 174 mg of 4-nitrobenzyl (1S,5R,6S)-2-(7-ethylthioimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate in the same manner as in Example 1-b), except that the;purification was carried out by column chromatography on Cosmosil 40C18-PREP (5% aqueous methanol).

NMR (D 2 O) δ (HOD=4.80 ppm): 1.15 (3H, t, J=7.3 Hz), 1.24 (3H, d, J=7.4 Hz), 1.32 (3H, J=6.2 Hz), 2.76 (2H, q, J=3 Hz), 3.45-3.6 (2H, m), 4.2-4.35 (2H, m), 7.88 (1H, s), 8.12 (1H, s).

›Example 133

Sodium (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(3-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(3-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 37 mg of 4-nitrobenzyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(3-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate was obtained from 743 mg of 4-nitrobenzyl (3R,5R,6S)-6-((1R)-1-hydroxyethyl)-2-oxo-1-carbapenam-3-carboxylate and 1.02 g of 3-methylthio-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 1.39 (3H, d, J=6.3 Hz), 2.31 (3H, s), 3.28 (2H, m), 3.39 (1H, m), 4.30 (1H, m), 4.42 (1H, m), 5.24 (1H, d, J=13.7 Hz), 5.38 (1H, d, J=13.7 Hz), 7.13 (1H, s), 7.50 (2H, d, J=9.1 Hz), 8.04 (1H, s), 8.14 (2H, d, J=9.1 Hz).

b) Sodium (5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(3-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-b), 15 mg of the title compound was obtained from 35 mg of 4-nitrobenzyl (5R,6S)-6-((1R)-1-hydroxyethyl)2-(3-methylthioimidazo[5,1-b]thiazol-2-yl-1-carbapen-2-em-3-carboxylate.

NMR (D 2 O) δ (HOD 4.65 ppm): 1.15 (3H, d, J=6.3 Hz), 2.22 (3H, s), 3.03 (1H, m), 3.26 (1H, m), 3.42 (1H, m), 4.12 (1H, m), 4.22 (1H, m), 6.96 (1H, s), 8.16 (1H, s).

›Example 134

Sodium (5R,6S)-2-(7-Ethylthioimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (5R,6S)-2-(7-Ethylthioimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 691 mg of 4-nitrobenzyl (5R,6S)-2-(7-ethylthioimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate was obtained from 869 mg of 4-nitrobenzyl (3R,5R,6S)-6-((1R)-1-hydroxyethyl)-2-oxo-1-carbapenam-3-carboxylate and 1.30 g of 7-ethylthio-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 1.25 (3H, t, J=7.3 Hz), 1.40 (3H, d, J=6.4 Hz), 2.83 (2H, q, J=7.3 Hz), 3.3-3.4 (3H, m), 4.25-4.4 (2H, m), 5.32 (1H, d, J=13.6 Hz), 5.55 (1H, d, J=13.6 Hz), 7.69 (2H, d, J=9.0 Hz), 8.02 (1H, s), 8.20 (1H, s), 8.25 (2H, d, J=9.0 Hz).

Sodium (5R,6S)-2-(7-Ethylthioimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

The title compound (60.7 mg) was obtained from 115 mg of 4-nitrobenzyl (5R,6S)-2-(7-ethylthioimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate in the same manner as in Example 1-b), except that the purification was carried out by column chromatography on Cosmosil 40C18-PREP (5% aqueous methanol).

NMR (D 2 O) δ (HOD=4.80 ppm): 1.16 (3H, t, J=7.4 Hz), 1.32 (3H, d, J=6.4 Hz), 2.77 (2H, q, J=7.4 Hz), 3.2-3.4 (2H, m), 3.45-3.55 (1H, m), 4.2-4.35 (2H, m), 7.72 (1H, s) 8.10 (1H, s).

›Example 135

Sodium (5R,6S)-6-((R)-1-Hydroxyethyl)-2-(3-methyl-7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (5R,6S)-6-((1R)-Hydroxyethyl)-2-(3-methyl-7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 927 mg of 4-nitrobenzyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(3-methyl-7-methylthioimidazo[5, 1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate was obtained from 1.044 g of 4-nitrobenzyl (3R,5R,6S)-6-((1R)-1-hydroxyethyl)-2-oxo-1-carbapenam-3-carboxylate and 1.56 g of 3-methyl-7-methylthio-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ 1.40 (3H, d, J=6.3 Hz), 2.19 (3H, s), 2.43 (3H, s), 3.1-3.3 (2H, m), 3.36 (1H, dd, J 1 =6.4 Hz, J 2 =3.1 Hz), 4.25-4.45 (2H, m), 5.24 (1H, d, J=13.7 Hz), 5.43 (1H, d, J=13.7 Hz), 7.57 (2H, d, J=8.7 Hz), 7.85 (1H, s), 8.18 (2H, d, J=8.7 Hz).

b) Sodium (5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(3-methyl-7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

The title compound (43.6 mg) was, obtained from 89.8 mg of 4-nitrobenzyl (5R,6S)-6-(,(1R)-1-hydroxyethyl)-2-(3-methyl-7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate in the same manner as in Example 1-b), except that the purification was carried out by column chromatography on Cosmosil 40C18-PREP (5% aqueous methanol).

NMR (D 2 O) δ (HOD=4.80 ppm): 1.31 (3H, d, J=6.3 Hz), 2.26 (3H, s), 2.36 (3H, s), 3.05-3.35 (2H, m), 3.55 (1H, dd, J 1 =5.7 Hz, J 2 =3.0 Hz), 4.2-4.4 (2H, m), 8.11 (1H, s).

›Example 136

Sodium (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfinyl-5-methylthioimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

a) 4-Nitrobenzyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfinyl-5-methylthioimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

4-Nitrobenzyl (1S,5R,6S)-2-[5,7-bis(methylthio)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (140 mg) was dissolved in 2.5 ml, of dichloromethane. m-Chloroperbenzoic acid (56 mg) was added to the solution. The mixture was stirred at room temperature for 15 min. An aqueous sodium thiosulfate solution (56 ml) was added thereto, followed by separation. The organic layer was washed with 10 ml of a semisaturated aqueous sodium hydrogencarbonate solution and 10 ml of semisaturated brine and then dried over anhydrous magnesium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by column chromatography on silica gel (dichloromethane:methanol=20:1) to give 97 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfinyl-5-methylthioimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers).

NMR (CDCl 3 ) δ: 1.30, 1.31 (total 3H, d each, J=7.3 Hz each), 1.39 (3H, d, J=6.3 Hz), 2.62, 2.63 (total 3H, s each), 2.95, 2.96 (total 3H, s each), 3.36 (1H, m), 3.47 (1H, m), 4.30 (1H, m), 4.36 (1H, m), 5.27 (1H, d, J=13.7 Hz), 5.53 (1H, d, J=13.7 Hz), 7.66 (2H, d, J=18.5 Hz), 8.23 (total 3H, m).

b) 4-Sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfinyl-5-methylthio-imidazo[5,1-b]thiazol-2-yl)-1-methyl1-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

In the same manner as in Example 1-b), 37 mg of the title compound was obtained from 97 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfinyl-5-methylthioimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate.

NMR (D 2 O) δ (HOD=4.65 ppm): 1.11 (3H, d, J=7.0 Hz), 1.17 (3H 1 , d, J=6.3 Hz), 2.37, 2.38 (total 3H, s each), 2.92, 2.93 (total 3H, s each), 3.37 (1H, m),l3.50 (1H, m), 4.16 (2H, m) 7.82, 7.84 (total 1H, s each).

›Example 137

Sodium (5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(3-hydroxymethyl-7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (5R,6S)-2-(3-t-Butyldimethylsilyloxymethyl-7-methylthioimidazo[5.1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 561 mg of 4-nitrobenzyl (5R,6S)-2-(3-t-butyldimethylsilyloxymethyl-7-methylthioimidazo-[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate was obtained from 522 mg of 4-nitrobenzyl (3R,5R,6S)-6-((1R)-1-hydroxyethyl)-2-oxo-1-carbapenam-3-carboxylate and 995 mg of 3-t-butyldimethylsilyloxymethyl 7-methylthio-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 0.01 (6H, s), 0.83 (9H, s), 1.39 (3H, d, J=6.3 Hz), 2.43 (3H, s), 3.1-3.2 (2H, m), 3.34 (1H, dd, J 1 =6.5 Hz, J 2 =3.0 Hz), 4.25-4.45 (2H, m), 4.49 (2H, s), 5.21 (1H, d, J=13.7 Hz), 5.41 (1H, d, J=13.7 Hz), 7.56 (2H, d, J=8.8 Hz), 8.07 (1H, s), 8.17 (2H, d, J=8.8 Hz).

b) 4-Nitrobenzyl (5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(3-hydroxymethyl-7-methylthio-imidazo[5.1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

4-Nitrobenzyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(3-hydroxymethyl-7-methylthio-imidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (315 mg) was obtained from 561 mg of 4-nitrobenzyl (5R,6S)-2-(3-t-butyldimethylsilyloxymethyl-7-methylthioimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate in the same manner as in Example 36-b), except that the purification was carried out by column chromatography on silica gel, (dichloromethane:methanol=20:1).

NMR (CDCl 3 ) δ: 1.39 (3H, d, J=6.3 Hz), 2.43 (3H, s), 3.1-3.25 (2H, m), 3.36 (1H, dd, J 1 =6.4 Hz, J 2 =3.1 Hz), 4.25-4.45 (2H, m), 4.45-4.6. (2H, m), 5.26 (1H, d, J=13.6 Hz), 5.47 (1H, d, J=13.6 Hz), 7.631 (2H, d, J=8.9 Hz), 8.18 (1H, s), 8.23 (2H, d, J=8.9 Hz).

c) Sodium (5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(3-hydroxymethyl-7-methylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

The title compound (59.4 mg) was obtained from 113 mg of 4-nitrobenzyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(3-hydroxymethyl-7-methylthio-imidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate in the same manner as in Example 1-b), except that the purification was carried out by column chromatography on Cosmosil 40C18-PREP (5% aqueous methanol).

NMR (D 2 O) δ (HOD=4.80 ppm): 1.35 (3H, d, J=6.4 Hz), 2.4.1 (3H, s), 3.1-3.35 (2H, m), 3.60 (1H, dd, J 1 =5.8 Hz, J 2 =3.0 Hz), 4.25-4.45 (2H, m), 4.69 9 (2H, s), 8.29 (1H, s).

›Example 138

Sodium (5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(3-phenylimidazo[5,1-b]thiazol-2-yl)-1-6carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(3-phenylimidazo[5,1-b]thiazol-2-yl-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 110 mg of 4-nitrobenzyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(3-phenylimidazo[5,1-b]thiazol6l-2-yl)-1-carbapen-2-em-3-carboxylate was obtained from 348 mg of 4-nitrobenzyl (3R,5R,6S)-6-((1R)-1-hydroxyethyl)-2-oxo-1-carbapenam-3-carboxylate and 513 mg of 3-phenyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 1.21 (3H, d), 2.90 (2H, m), 3.18 (1H, dd), 4.22 (2H, m), 5.16 (1H, d), 5.32 (1H, d), 7.12 (1H, s), 7.50 (7H, m), 7.92 (1H, s), 8.15 (2H, d).

b) Sodium (5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(3-phenylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

The title compound (11 mg) was obtained from 100 mg of 4-nitrobenzyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(3-phenylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate in the same manner as in Example 1-b), except that the purification was carried out by column chromatography on Cosmosil 40C18-PREP (30% aqueous methanol).

NMR (D 2 O) δ (HOD=4.80 ppm): 1.23!(3H, d), 2.85 (2H, m), 3.37 (1H, m), 4.18 (2H, m), 7.12 (1H, s), 7.56 (5H, s), 8.11 (1H, s).

›Example 139

Sodium (5R,6S)-2-(7-Aminoacetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (5R,6S)-6-((1R)-1-Hydroxyethyl)-2-[7-(4-nitrobenzyloxycarbonyl-amino)acetylimidazo[5,1-b]thiazol-2-yl]-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 195 mg of 4-nitrobenzyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-[7-(4-nitrobenzyloxycarbonylamino)acetyl-imidazo[5,1-b]thiazol-2-yl]-1-carbapen-2-em-3-carboxylate was obtained from 348 mg of 4-nitrobenzyl (3R,5R,6S)-6-((1R)-1-hydroxyethyl)-2-oxo-1-carbapenam-3-carboxylate and 650 mg of 7-(4-nitrobenzyloxycarbonylamino)acetyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (DMSO-d 6 ) δ: 1.18 (3H, d), 3.151 (3H, m), 4.28 (1H, m), 4.47 (3H, m), 5.17 (1H, d), 5.21 (2H, s), 5.51 (2H, ABq), 7.65 (2H, d), 7.77 (2H, d), 8.24. (2H, d), 8.26 (2H, d), 8.37 (1H, s), 8.52 (1H, s).

b) Sodium (5R,6S)-2-(7-Aminoacetylimidazo-[5-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl1)-1-carbapen-2-em-3-carboxylate

The title compound (34 mg) was obtained from 140 mg of 4-nitrobenzyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-[7-(4-nitrobenzyloxycarbonyl-amino)acetylimidazo[5,1-b]thiazol-2-yl]-1-carbapen-2-em-3-carboxylate in the same manner as in Example 1-b), except that the purification was carried out by column chromatography on Cosmosil 40C18-PREP (10% aqueous methanol).

NMR (D 2 O) δ (HOD=4.80 ppm): 1.31 (3H, d), 3.08 (2H, m), 3.50 (1H, dd), 4.23 (2H, m), 4.39 (2H, s), 7.57 (1H, s), 7.9.9. (1H, s).

›Example 140

Sodium (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(5-methanesulfinylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

a) 4-Nitrobenzyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(5-methanesulfinylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers)

4-Nitrobenzyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(5-methanesulfinylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers) (95 mg) was obtained in the same manner as in Example 136-a), except that the reaction was carried out using 112 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(5-methylthioimidazo-[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate and 49 mg of m-chloroperbenzoic acid as the starting compounds.

NMR (CDCl 3 ) δ 1.32 (3H, d, J=7.3 Hz), 1.39 (3H, d, J=6.3 Hz), 3.12 (3H, s), 3.38 (1H, m), 3.56 (1H, m), 4.36 (2H, m), 5.29 (1H, d, J=13.6 Hz), 5.53 (1H, d, J=13.6 Hz), 7.67 (2H, d, J=8.8 Hz), 8.23 (2H, d, J=8.8 Hz), 8.58, 8.59 (total 1H, s each).

b) Sodium (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(5-methanesulfinylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example 1-b), 44 mg of the title compound was obtained from 95 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(5-methanesulfinylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate.

NMR (D 2 O) δ (HOD=4.65 ppm): 1.:16 (3H, m), 1.22 (3H, d, J=6.5 Hz), 3.11 (3H, s), 3.44 (1H, m), 3.54 (1H, m), 4.20 (2H, m), 7.20, 7.21 (total 1H, s each), 8.08 (1H, s).

›Example 141

Sodium (1S,5R,6S)-2-(51.7-Dimethanesulfinyliidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

a) 4-Nitrobenzyl (1S,5R,6S)-2-(5,7-Dimethanesulfinylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers).

4Nitrobenzyl (1S,5R,6S)-2-(5,7-dimethanesulfinylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers) (95 mg) was obtained in the same manner as in Example 136-a), except that the reaction was carried out using 129 mg of 4-nitrobenzyl (1S,5R,6S)-2-[5,7-bis(methylthio)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate and 99 mg of m-chloroperbenzoic acid as the starting compounds.

NMR (CDCl 3 ) δ: 1.31 (3H, d, J=7.3 Hz), 1.38 (3H, d, J=6.4 Hz), 2.96 (3H, m), 3.15 (3H, m), 3.38 (1H, m), 3.54 (1H, in),4.31 (1H, m), 4.39 (1H, dd, J 1 =9.7 Hz, J 2 =2.7 Hz), 5.29 (1H, d, J=13.4 Hz), 5.43 (1H, d, J=13.4 Hz), 7.67 (2H, d, J=9.1 Hz), 8.23 (2H, d, J=9.1 Hz), 8.66 (1H, m).

b) Sodium (1S,5R,6S)-2-(5,7-Dimethanesulfinylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-(1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example 1-b), 30 mg of the title compound was obtained from 59 mg of 4-nitrobenzyl (1S,5R,6S)-2-(5,7-dimethanesulfinylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate.

NMR (D 2 O) δ (HOD=4.65 ppm): 1.16 (3H, m), 1.21 (3H, d, J=6.3 Hz), 3.01 (3H, m), 3.14 (3H, s), 3.44 (1H, m), 3.58 (1H, m), 4.19 (2H, m), 8.20 (1H, m).

›Example 142

Sodium (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(5-methanesulfinyl-7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers).

a) 4-Nitrobenzyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(5-methanesulfinyl-7-methanesulfonylimidazo[5,1-b]thiazol-2yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

4-Nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(5-methanesulfinyl-7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers) (53 mg) was obtained in the same manner as in Example 136-a), except that the reaction was carried out using 130 mg of 4-nitrobenzyl (1S,5R, 6S)-2-[5,7-bis(methylthio)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-21-em-3-carboxylate and 135 mg of m-chloroperbenzoic acid as the starting compounds.

NMR (CDCl 3 ) δ: 1.32 (3H, d, J=7.4 Hz), 1.39 (3H, d, J=6.3 Hz), 3.18, 3.19 (total 3H, s each), 3.21, 3.21 (total 3H, s each), 3.39 (1H, dd, J=6.3 Hz, J 2 =2.9 Hz), 3.56 (1H,: m), 4.32 (1H, m), 4.40 (1H, dd, J 1 =9.3 Hz, J 2 =2.7 Hz), 5.29 (1H, d, J=13.6 Hz), 5.53 (1H, d, J=13.6 Hz), 7.67 (2H, d, J=8.5 Hz), 8.24 (2H, d, J=8.5 Hz), 8.65, 8.67 (total 1H, s each).

b) Sodium (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(5-methanesulfonyl-7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example 1-b), 23 mg of the title compound was obtained from 53 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(5-methanesulfinyl-7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate.

NMR (D 2 O) δ (HOD=4.65 ppm): 1.15, 1.16 (total 3H, d each, J=7.2 Hz), 1.21 (3H, d, J=6.3 Hz), 3.14 (3H, s), 3.23, 3.24 (total 3H, s each), 3.44 (1H, dd, J 1 =5.8 Hz, J 2 =2.0 Hz), 3.57 (1H, m), 4.16 (1H, m), 4.23 (1H, m), 8.20, 8.21 (total 1H, s each).

›Example 143

Sodium (1S,5R,6S)-2-[5,7-bis(Methanesulfonyl)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (1S,5R,6S)-2-[5,7-bis(Methanesulfonyl)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

4-Nitrobenzyl (1S,5R,6S)-2-[5,7-bis(methanesulfonyl)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (107 mg) was obtained in the same manner as in Example 44-b), the reaction was carried out using 102 mg of 4-nitrobenzyl (1S,S5R,6S)-2-[5,7-bis(methylthio)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate and 448 mg of oxone as the starting compounds. The reaction product was purified by column chromatography on silica gel (dichloromethane:methanol=20:1 to 10:1).

NMR (CDCl 3 ) δ: 1.33 (3H, d, J=7.3 Hz), 1.35 (3H, d, J=6.3 Hz), 3.25 (3H, s), 3.38 (1H, m), 3.41 (3H, s), 3.59 (1H, m), 4.35 (1H, m), 4.43 (1H, dd, J 1 =9.7 Hz J 2 =2.9 Hz), 5.30 (1H, d, J=13.8 Hz), 5.54 (1H, d, J=13.8 Hz), 7.69 (2H, d, J=9.3 Hz), 8.22 (2H, d, 9.3 Hz), 8.56 (1H, s).

b) Sodium (1S,5R,6S)-2-[5,7-bis(Methanesulfonyl)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-6m-3-carboxylate

In the same manner as in Example 1-b), 20 mg of the title compound was obtained from 67 mg of 4-nitrobenzyl (1S,5R,6S)-2-[5,7-bis(methanesulfonyl)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate.

NMR (D 2 O) δ ((HOD=4.65 ppm): 1.14 (3H, d, J=7.3 Hz), 1.26 (3H, d, J=6.6 Hz), 3.25 (3H, s), 3.35 (3H, s), 3.44 (1H, dd, J=6.1 Hz, J 2 27 Hz), 3.59 (1H, m), 4.16 (1H, m), 4.23 (1H, dd, J 1 =9.5 Hz, J 2 =21.7 Hz), 818 (1H, s).

›Example 144

Sodium (5R,6S)-2-(3-Aminomethylimidazo[b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (5R,6S)-2-(3-Aminomethylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 268.2 mg of 4-nitrobenzyl (5R,6S)-2-(3-azidomethylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate was obtained from 348 mg of 4-nitrobenzyl (3R,5R,6S)-6-((1R)-1-hydroxyethyl)-2-oxo-1-carbapenam-3-carboxylate and 515 mg of 3-azidomethyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 1.38 (3H, d, J=6.3 Hz), 3.1-3.3 (2H, m), 3.40 (1H, dd, J 1 =6.1 Hz, J 2 =3.0 Hz), 4.25-4.35 (1H, m), 4.36 (2H, s), 4.4-4.5 (1H, m), 5.21 (1H, d, J=13.5 Hz), 5.41 (1H, d, J=13.5 Hz); 7.12 (1H, s), 7.53 (2H, d, J=8.5 Hz), 8.03 (1H, s), 8.15 (2H, d, J=8.5 Hz).

b) Sodium (5R,6S)-2-(3-Aminomethylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

The title compound (22.1 mg) was obtained from 97.4 mg of 4-nitrobenzyl (5R,6S)-2-(3-azidomethylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate in the same manner as in Example 1-b), except that the purification was carried out by column chromatography on Cosmosil 40C18 PREP (10% aqueous methanol).

NMR (D 2 O) δ (HOD=4.80 ppm): 1.29 (3H, d, J=6.1 Hz), 3.1-3.4 (2H, m), 3.5-3.6 (1H, m), 4.2-4.4 (2H, m), 4.34 (2H,s), 7.12 (1H, s), 8.32 (1H, s).

›Example 145

Sodium (5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(3-hydroxymethylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (5R,6S)-2-(3-t-Butyldimethylsilyloxymetbylimidazo[5 1-b]thiazol-2-yl)-6-((1R)1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 1.396 g of 4-nitrobenzyl (5R,6S)-2-(3-t-butyldimethylsilyloxymethylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate was obtained from 1.42 g of 4 nitrobenzyl (3R,5R,6S)-6-((1R)-1-hydroxyethyl)-2-oxo-1-carbapenam-3-carboxylate and 2.28 g of 3-t-butyldimethylsilyloxymethyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 0.00 (6H, s), 0.84 (9H, s), 1.40 (3H, d, J=6.3 Hz), 3.1-3.3 (2H, m), 3.33 (1H, dd, J 1 =6.3 Hz, J 2 =2.9 Hz), 4.25-4.45 (2H, m), 4.52 (2H, s), 5.23 (1H, d, J=13.4 Hz), 5.42 (1H, d, J=13.4 Hz), 7.08 (1H, s), 7.55 (2H, d, J=8.9 Hz), 8.10 (1H, s), 8.17 (2H, d, J=8.9 Hz).

b) 4-Nitrobenzyl (5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(3-hydroxymethylimidazo[5;1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

4-Nitrobenzyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(3-hydroxymethylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (507 mg) was obtained from 1.396 g of 4-nitrobenzyl (5R,6S)-2-(3-t-butyldimethylsilyloxymethyl-1-imidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate in the same manner as in Example 36-b), except that the purification was carried, out using Sephadex LH-20 (chloroform:methanol=1:1).

NMR (CDCl 3 ) δ: 1.39 (3H, d, J=6.3 Hz), 3.1-3.3 (2H, m), 3.36 (1H, dd, J 1 =6.5 Hz, J 2 =2. 9 Hz), 4.25-4.45 (2H, m), 4.5-4.65 (2H, m), 5.27 (1H, d, J=13.4 Hz), 5.47 (1H, d, J=13.4 Hz), 7.10 (1H, s), 7.63 (2H, d, J=8.8 Hz), 8.20 (1H, s), 8.23 (2H, d, J=8.8 Hz).

c) Sodium (5R,6S)-6-((1R)-1-Hydroxymethylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

The title compound (58.4 mg) was obtained from 145.5 mg of 4-nitrobenzyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(3-hydroxymethylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate in the same manner as in Example 1-b), except that the purification was carried out by column chromatography on Cosmosil 40C18-PREP (5% aqueous methanol).

NMR (D 2 O) δ (HOD=4.80 ppm): 1.29 (3H, d, J=6.4 Hz), 3.13 (1H, dd, J 1 =17.4 Hz, J 2 =10.1 Hz), 3.28 (1H, dd, J 1 =7.4 Hz, J 2 =8.5 Hz), 3.55 (1H, dd, J 1 =5.8 Hz, J 2 =2.9 Hz), 4.2-4.4 (2H, m), 4.66 (2H, s), 7.08 (1H, s), 8.25 (1H, s).

›Example 146

Sodium (5g,6S)-2-[5.7-bis(Methylthio)-imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (5R,6S)-2-[5,7-bis(Methylthio)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 810 mg of 4-nitrobenzyl (5R,6S)-2-[5,7-bis(methylthio)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate was obtained from 803 mg of 4-nitrobenzyl (3R,5R,6S)-6-((1R)-1-hydroxyethyl)-2-oxo-1-carbapenam-3-carboxylate and 1.18 g of 5,7-bis(methylthio)-2-(tri-n-butylstannyl)imidazo-[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 1.39 (3H, d, J=6.3 Hz), 2.42 (3H, s), 2.58 (3H, s), 3.30-3.40 (total 3H, m), 4.29-4.37 (total 2H, m), 5.33 (1H, d, J=13.6 Hz), 5.56 (1H,d, J=13.6 Hz), 7.69 (2H, d, J=9.0 Hz), 7.96 (1H, s), 8.25 (2H1, d, J=9.0 Hz).

b) Sodium (5R,6S)-2-[5,7-bis(Methylthio)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-b), 33 mg of the title compound was obtained from 78 mg of 4-nitrobenzyl (5R,6S)-2-[5,7-bis(methylthio)-imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate.

NMR (D 2 O) δ (HOD=4.65 ppm): 1.20 (3H, d, J=6.3 Hz), 2.24 (3H, s), 2.35 (3H1, s), 3.18 (2H, m), 3.42 (1H, dd, J 1 =6.1 Hz, J 2 =1.9 Hz), 4.14-4.21 (2H, m), 7.55 (1H, s).

›Example 147

Sodium (1S,5R,6S)-2-(5-Acetyl-7-methylthioimidazo[5,1-b]thiazol-2yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (1S,5R,6S)-2-(5-Acetyl-7-methylthioimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 168 mg of 4-nitrobenzyl (1S,5R,6S)-2-(5-acetyl-7-methylthioimidazo-[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate was obtained from 211 mg of 4-nitrobenzyl (1R,3R,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-oxo-1-carbapenam3-carboxylate and 280 mg of 5-acetyl-7-methylthio-2-(tri-n-butylstannyl)-imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 1.34 (3H, d, J=7.3 Hz), 1.40 (3H, d, J 1 =6.1 Hz), 2.51 (3H, s), 2.66 (3H, s), 3.39 (1H, m), 3.66 (1H, m), 4.33 (1H, m), 4.39 (1H, dd, J 1 =9.5 Hz, J 2 =2.7 Hz), 5.31 (1H, d, J=13.6 Hz), 5.55 (1H d, J=13.6 Hz), 7.68 (2H, d, J=8.7 Hz), 8.24 (2H, d, J=8.7 Hz), 8.81 (1H, s).

b) Sodium (1S,5R,6S)-2-(5-Acetyl-7-methylthioimidazo[5,1-b]thiazol-2-yl-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-b), 29 mg of the title compound was obtained from 54 mg of 4-nitrobenzyl (1S,5R,6S)-2-(5-acetyl-7-methylthio-imidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate.

NMR (D 2 O) δ (HOD=4.65 ppm): 1.14 (3H, d, J=7.3 Hz), 1.23 (3H, d, J=6.3 Hz), 2.35 (3H, s), 2.47 (3H, s), 3.42-30 (1NH, m), 3.55 (1H, m), 4.18 (1H, m), 4.25 (1H, m), 8.30 (1H, s).

›Example 148

Sodium (1S,5R,6S)-2-[3,7-bis(Methylthio)-imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (1S,5R,6S)-2-[3,7-bis(Methylthio)imidazo[5,1-b]thiazol-2-yl-1]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-m-3-carboxylate

In the same manner as in Example 1-a), 489 mg of 4-nitrobenzyl (1S,5R,6S)-2-[3,7-bis(methylthio)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate was obtained from 724 mg of 4-nitrobenzyl (1R,3R,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-oxo1carbapenam-3-carboxylate and 1.11 g of 3,7-bis(methylthio)-2-(tri-n-butylstannyl)-imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 1.22 (3H, d, J=7.4 Hz), 1.39 (3H, d, J=6.2 Hz), 2.28 (3H, s), 2.46 (3H, s), 3.4-3.5 (2H, m), 4.3-4.4 (1H, m), 4.48 (1H, dd, J 1 =110.4 Hz, J 2 =3.3 Hz), 5.21 (1H, d, J=13.4 Hz), 5.41 (1H, d, J=13.4 Hz), 7.53 (2H, d, J=8.8 Hz), 8.03 (1H, s), 8.16 (2H, d, J=8.8 Hz).

b) Sodium (1S,5R,6S)-2-[3,7-bis(Methylthio)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

The title compound (70.6 mg) was obtained from 157 mg of 4-nitrobenzyl (1S,5R,6S)-2-[3,7-bis(methylthio)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate in the same manner as in Example 1-b), except that the purification was carried out by column chromatography on Cosmosil 40C18-PREP (10% aqueous methanol).

NMR (D 2 O) δ (HOD=4.80 ppm): 1.13 (3H, d, J=7.2 Hz), 1.31 (3H, d, J=6.4 Hz), 2.34 (3H, s), 2.36 (3H, s), 3.35-3.5 (1H, m) 3.54 (1H, dd, J 1 =5.9 Hz, J 2 =3.0 Hz), 4.2-4.35 (1H, m), 4.37 (1H, dd, J 1 =9.9 Hz, J 2 =2.9 Hz), 8.30 (1H, s).

›Example 149

Sodium (1S5R,6S)-2-(5-Acetyl-7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (1S,5R,6S)-2-(5-Acetyl-7-methanesulfonylimidazo[5,1-b]thiazol2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

4-Nitrobenzyl (1S,5R,6S)-2-(5-acetyl-7-methanesulfonylimidazo[5,1-b]thiazol2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (54 mg) was obtained in the same manner as in Example 44-b), except that 52 mg of 4-nitrobenzyl (1S,5R,6S)-2-(5-acetyl-7-methylthioimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate and 115 mg of oxone were used as the starting compounds. The reaction product was purified by column chromatography on silica gel (dichloromethane:methanol=20:1 to 10:1).

NMR (CDCl 3 ) δ: 1.34 (3H, d, J=7.3 Hz), 1.40 (3H, d, J=6.1 Hz), 2.71 (3H, s), 3.26 (3H, s), 3.40 (1H, m), 3.64 (1H, m), 4.33 (1H, m), 4.43 (1H, dd, J 1 =9.7 Hz, J 2 =1.9 Hz), 5.31 (1H, d, J=13.4 Hz), 5.54 (1H, d, J=13.4 Hz), 7.68 (2H, d, J=9.1 Hz), 8.24 (2H, d, J=9.1 Hz), 8.80 (1H, s).

b) Sodium (1S,5R,6S)-2-(5-Acetyl-7-methanesulfonylimidazo[5,1-b]thiazol2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in 1-b), 15 mg of the title compound was obtained from 53 mg of 4-nitrobenzyl (1S,5R,6S)-2-(5-acetyl-7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate.

NMR (D 2 O) δ (HOD 4.65 ppm): 1.12 (3H, d, J=7.3 Hz), 1.20 (3H, d, J=6.4 Hz), 2.54 (3H, s), 3.24 (3H, s), 3.42 (1H, dd, J 1 =6.2 Hz, J 2 =2.8 Hz), 3.60 (1H, m), 4.15 (1H, m), 4.22 (1H, dd, J 1 =9.3 Hz, J 2 =2.7 Hz), 8.43 (1H, s).

›Example 150

Sodium (1S,5R,6S)-2-(5-bromo-7-Methylthioimidazo[5,1-b]thiazol-2-yl-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (1S,5R,6S)-2-(5-Bromo-7-methylimidazo[5.1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

4Nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo-[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (77 mg) was dissolved in 5 ml of benzene at room temperature. N-bromosuccinimide (33 mg) and 5 mg of 2, 2′-azobis(isobutyronitrile) were added to the solution. The mixture was stirred for 10 min. Dichloromethane (10 ml) and 10 ml of semisaturated brine were added thereto, followed by separation. The organic layer was dried over anhydrous magnesium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by column chromatography on silica gel (dichloromethane:methanol=20:1) to give 70 mg of 4-nitrobenzyl (1S,5R,6S)-2-(5-bromo-7-methylthioimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate.

NMR (CDCl 3 ) δ: 1.31 (3H, d, J=7.3 Hz), 1.40 (3H, d, J=6.3 Hz), 2.43 (3H, s), 3.38 (1H, m), 3.48 (1H, m), 4.32 (1H, m), 4.38 (1H, dd, J 1 =9.8 Hz, J 2 =2.7 Hz), 5.29 (1H, d, J=13.4 Hz), 5.55 (1H, d, J=13.4 Hz), 7.68 (2H, d, J=8.5 Hz), 8.03 (1H, s), 8.25 (2H, d, J=8.5 Hz).

b) Sodium (1S ,5R ,6S)-2-(5-Bromo-7-methylthioimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-b), 14 mg of the title compound was obtained from 68 mg of 4-nitrobenzyl (1S,5R,6S)-2-(5-bromo-7-methylthioimidazo[5,1-b]thiazol-2-yl)-6((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate.

NMR (D 2 O) δ (HOD=4.65 ppm): 1.12 (3H, d, J=7.3 Hz), 1.19 (3H, d, J=6.4 Hz), 2.23 (3H, s), 3.40 (1H, dd, J 1 =9.8 Hz, J 2 =2.7 Hz), 3.48 (1H, m), 4.13-4.22 (1H, m), 7.60 (1H, s).

›Example 151

Sodium (5R,6S)-2-(5-Acetyl-7-methylthioimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (5R,6S)-2-(5-Acetyl-7-methylthioimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 147 mg of 4-nitrobenzyl (5R,6S)-2-(5-acetyl-7-methylthioimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate was obtained from 174 mg of 4-nitrobenzyl (3R,5R,6S)-6-((1R)-1-hydroxyethyl)-2-oxo-1-carbapenam-3-carboxylate and 250 mg of 5-acetyl-7-methylthio-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 1.40 (3H, d, J=6.3 Hz), 2.51 (3H, s), 2.66 (3H, s), 3.33-3.52 (total 3H, m), 4.29-4.40 (total 2H, m), 5.34 (1H, d, J=13.4 Hz), 5.57 (1H, d, J=13.4 Hz), 7.70 (2H, d, J=8.7 Hz), 8.25 (2H, d, J=8.7 Hz), 8.67 (1H, s).

b) Sodium (5R,6S)-2-(5-acetyl-7-methylthioimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-b), 21 mg of the title compound was obtained from 80 mg of 4-nitrobenzyl (5R,6S)-2-(5-acetyl-7-methylthioimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate.

NMR (D 2 O) δ (HOD=4.65 ppm): 1.21 (3H, d, J=6.4 Hz), 2.29 (3H, s), 2.35 (3H, s), 2.95-3.14 (2H, m), 3.46 (1H, dd, J 1 =6.1 Hz, J 2 =2.9 Hz), 4.10-4.18 (2H, m), 7.52 (1H, s).

›Example 152

Sodium (1S,5R,6S)-2-(5-Cyano-7-methylthioimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

a)4-Nitrobenzyl (1S,5R,6S)-2-(5-Cyano-7-methylthioimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 91 mg of 4-nitrobenzyl (1S,5R,6S)-2-(5-cyano-7-methylthioimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate was obtained from 181 mg of 4-nitrobenzyl (1R,3R,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-oxo-1-carbapenam-3-carboxylate and 238 mg of 5-cyano-7methylthio-2-(tri-n-butylstannyl)-imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 1.34 (3H, d, J=7.3 Hz), 1.40 (3H, d, J=6.1 Hz), 2.51 (3H, s), 3.40 (1H, m), 3.54 (1H, m), 4.32 (1H, m), 4.42·(1H, dd, J 1 =9.5 Hz, J 2 =2.8 Hz), 5.31 (1H, d, J=13.7 Hz), 5.54 (1H, d, J=13.7 Hz), 7.69 (2H, d, J=8.2 Hz), 8.26 (total 3H, m).

b) Sodium (1S,5R,6S)-2-(5-Cyano-7-methylthioimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-b), 19 mg of the title compound was obtained from 61 mg of 4-nitrobenzyl (1S,5R,6S)-2-(5-cyano-7- methylthioimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl1-carbapen-2-em-3-carboxylate.

NMR (DMSO-d 6 ) δ: 1.10 (3H, d, J= 7.1 Hz), 1.16 (3H, d, J=6.4 Hz), 2.41 (3H, s), 3.11 (1H, dd, J 1 =6.8 Hz, J 2 =2.6 Hz), 3.56 (1H, m), 3.92 (1H, m), 4.03 (1H, dd, J 1 =9.2 Hz, J 2 =2.7 Hz), 5.01 (1H, d, J=5.1 Hz), 8.31 (1H, s).

›Example 153

Sodium (5R,6S)-2-[3,7-bis(Methylthio)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (5R,6S)-2-[3,7-bis (Methylthio)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 360 mg of 4-nitrobenzyl (5R,6S)-2-[3,7-bis(methylthio)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate was obtained from 645 mg of 4-nitrobenzyl (3R,5R,6S)-6-((1R)-1-hydroxyethyl)-2l-oxo-1-carbapenam-3-carboxylate and 990 mg of 3,7-bis(methylthio)-2-(tri-n-butylstannyl)imidazo-[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 1.40 (3H, d, J=6.3 Hz), 2.31 (3H, s), 2.44 (3H, S), 3.2-3.4 (2H, m), 3.41 (1H, dd, J 1 =6.5 Hz, J 2 =3.1 Hz), 4.25-4.4 (1H, m), 4.4-4.5 (1H, m), 5.25 (1H, d, J=13.3 Hz), 5.40 (1H, d, J=13.3 Hz), 7.53 (2H, d, J=8.8 Hz), 8.02 (1H, s), 8.15 (2H, d, J=8.8 Hz)

b) Sodium (5R,6S)-2-[3,7-bis(methylthio)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

The title compound (74.1 mg) was obtained from 145.7 mg of 4-nitrobenzyl (5R,6S)-2-[3,7-bis(methylthio)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate in the same manner as in Example 1-b), except that the purification was carried out by column chromatography on Cosmosil 40C18-PREP (5% aqueous methanol).

NMR (D 2 O) δ (HOD=4.80 ppm): 1.30 (3H, d, J=6.5 Hz), 2.35 (6H, 2s), 3.16 (1H, dd, J 1 =17.1 Hz, J 2 =10.2 Hz), 3.41 (1H;, dd, J 1 =17.1 Hz, J 2 =8.3 Hz), 3.57 (1H, dd, J 1 =5.8 Hz, J 2 =2.8 Hz), 4.2-4.4 (2H, m), 8.28 (H, s)

›Example 154

Sodium (1S,5R,6S)-2-(5-Chloro-7-methylthioimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (1S,5R,6S)-2-(5-Chloro-7-methylthioimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

4 Nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo-[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (109 mg) was dissolved in 10 ml of benzene at room temperature. N-Chlorosuccinimide (30 mg) and 5 mg: of 2, 2′-azobis(isobutyronitrile) were added to the solution. The mixture was stirred for 10 min. Dichloromethane (10 ml) and 10 ml of semisaturated brine were added thereto, followed by separation. The organic layer was dried over anhydrous magnesium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by column chromatography on silica gel (dichloromethane:methanol=20:1) to give 32 mg of 4-nitrobenzyl (1S,5R,6S)-2-(5-chloro-7-methylthioimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate.

NMR (CDCl 3 ) δ: 1.34 (3H, d, J=7.3 Hz), 1.40 (3H, d, J=6.1 Hz), 2.51 (3H, s), 3.40 (1H, m), 3.54 (1H, m), 4.32 (1H, m), 4.42 ·(1H, dd, J 1 =9.5 Hz, J 2 =2.8 Hz), 5.31 (1H, d, J=13.7 Hz), 5.54 (1H, d, J=13.7 Hz), 7.69 (2H, d, J=8.2 Hz), 8.26 (3H, m).

b) Sodium (1S,5R,6S)-2-(5-Chloro-7-methylthioimidazo[5,1-b]thiazol-2-yl )-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-b), 2 mg of the title compound was obtained from 30 mg of 4-nitrobenzyl (1S,5R,6S)-2-(5-chloro-7-methylthioimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate.

NMR (D 2 O) δ (HOD=4.65 ppm): 1.10(3H, d, J=7.3 Hz), 1.18 (3H, d, J=6.3 Hz), 2.21 (3H, s), 3.36-3.48 (2H, m), 4.10-4.20 (2H, m), 7.60 (1H, s).

›Example 155

Sodium (5R,6S)-2-(5-Cyano-7-methylthioimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl 1(5R,6S)-2-(5-Cyano-7-methylthioimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen -2-em-3-carboxylate

In the same manner as in Example, 1-a), 189 mg of 4-nitrobenzyl (5R,6S)-2-(5-cyano-7-methylthioimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate was obtained from 188 mg of 4-nitrobenzyl (3R,5R,6S)-6-((1R)-1-hydroxyethyl)-2-oxo-1-carbapenam-3-carboxylate and 262 mg of 5-cyano-7-methylthio-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 1.40 (3H, d, J=6.3 Hz), 2.51 (3H, s), 3.34-3.42 (3H, m), 4.29-4.42 (2H, m), 5.34 (1H, d, J=13.5 Hz), 5.56 (1H, d, J=13.5 Hz), 7.71(2H, d, J=8.0 Hz), 8.10 (1H, s), 8.26 (2H, d, J=8.0 Hz)

b) Sodium 5R,6S)-2-(5-Cyano-7-methylthioimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-b), 36 mg of the title compound was obtained from 94 mg of 4-nitrobenzyl (5R,6S)-2-(5-cyano-7-methylthioimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate.

NMR (D 2 O) δ (HOD=4.65 ppm): 1.18 (3H, d, J=6.6 Hz), 2.31 (3H, s), 3.17 (2H, m), 3.41 (1H, dd, J 1 =6.0 Hz, J 2 =13.0 Hz), 4.10-4.20 (2H, m), 7.77 (1H, s)

›Example 156

Sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-[7-(1propyl)thioimidazo[5,1-b]thiazol-2-yl]-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (1S,5R 6S)-6-((1R)-1-Hydroxyethyl)-1-methyl-2-[7-(1-propyl)thio-imidazo[5,1-b]thiazol-2-yl ]-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 369 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1- methyl-2-[7-(1-propyl)thio-imidazo[5,1′-b]thiazol-2-yl]-1-carbapen-2-em-3-carboxylate was obtained from 724 mg of 4-nitrobenzyl (1R,3R,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-oxo-1-carbapenam-3-carboxylate and 1.07 g of 7-(1-propyl)thio-2-(tri-n-butylstannyl)imidazo-[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 0.99 (3H, t, J=7.4 Hz), 1.31 (3H, d, J=7.1 Hz), 1.40 (3H, d, J=6.3 Hz), 1.5-1.7 (2H, m), 2.75-2.85 (2H, m), 3.37 (1H, dd, J 1 =6.3 Hz, J 2 =2.7 Hz), 3.4-3.55 (1H, m), 4.3-4.4 (2H, m), 5.28 (1H, d, J=13.7 Hz), 5.53 (1H, d, J=13.7 Hz), 7.68 (2H, d, J=8.5 Hz), 8.02 (1H, s), 8.25 (2H, d, J=8.5 Hz), 8.31 (1H, s)

b) Sodium (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-1-methyl-2-b7-(1-propyl)thio-imidazo[5,1-b]thiazol-2-yl]-1-carbapen-2-em-3-carboxylate

The title compound (58.2 mg) was obtained from 132 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-[7-(1-propyl)thio-imidazo[5,1-b]thiazol-2-yl]-1-carbapen-2-em-3-carboxylate in the same manner as in Example 1-b), except that the purification was carried out by column chromatography on Cosmosil 40C18-PREP (10% aqueous methanol).

NMR (D 2 O) δ (HOD=4.80 ppm): 0.93 (3H, t, J=7.2 Hz), 1.23 (3H, d, J=7.3 Hz), 1.21 (3H, d, J=6.3 Hz), 1.4-1.6 (2H, m, 2.65-2.75 (2H, m), 3.45-3.6 (2H, m), 4.2-4.35 (2H, m), 7.86 (1H, s), 8.09 (1H, s)

›Example 157

Sodium (5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-(1-propyl)thioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-(1-propyl)thioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 396 mg of 4-nitrobenzyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-(1-propyl)thioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate was obtained from 524 mg of 4-nitrobenzyl (3R,5R,6S)-6-((1R)-1-hydroxyethyl)-2-oxo-1-carbapenam-3-carboxylate and 770 mg of 7-(1-propyl)thio-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 0.98 (3H, t, J=7.4 Hz), 1.40 (3H, d, J=6.2:Hz), 1.55-1.7 (2H, m), 2.75-2.85 (2H, m), 3.3-3.4 (3H, m), 4.25-4.4 (2H, m), 5.32 (1H, d, J=13.5 Hz), 5.55 (1H, d, J=13.5 Hz), 7.70(2H, d, J=8.9 Hz), 8.01 (1H, s), 8.21 (1H, s), 8.25 (2H, d, J=8.5 Hz).

b) Sodium (5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-(1-propyl)thioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3 carboxylate

The title compound (72.3 mg) was obtained from 161 mg of 4-nitrobenzyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-(1-propyl)thioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate in the same manner as in Example 1-b), except that the purification was carried out by column chromatography on Cosmosil 40C18PREP (10% aqueous methanol).

NMR (D 2 O) δ (HOD=4.80 ppm): 0.92 (3H, t, J=7.4 Hz), 1.31 (3H, d, J=6.3 Hz), 1.4-1.55 (2H, m), 2.72 (2H, t, J7.2 Hz), 3.15-3.3 (2H, m), 3.49 (1H, dd, J 1 =6.1 Hz, J 2 =3.0 Hz), 4.2-4.3 (2H, m), 7.66 (1H, s), 8.04 (1H, s).

›Example 158

Sodium (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-isopropylthioimidazo[5,1-b]thiazol-2yl)-1-methyl-1-carbapen-2-em-3-carboxylate

a) 4-Nitrobenzyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-isopropylthioimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 557 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-isopropylthioimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate was obtained from 629 mg of 4-nitrobenzyl (1R,3R,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-oxo-1-carbapenam-3-carboxylate and 890 mg of 7-isopropylthio-2-(tri-n-butylstannyl)imidazo-[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 1.28 (6H, d, J=6.7 Hz), 1.31 (3H, d, J=7.2 Hz), 1.40 (3H, d, J=6.3 Hz), 3.28 (1H, sept, J=6.7 Hz), 3.37 (1H, dd, J 1 =6.6 Hz, J 2 =2.9 Hz), 3.4-3.5 (1H, m), 4.3-4.4 (2H, m), 5.28 (1H, d, J=13.7 Hz), 5.53 (1H, d, J=13.7 Hz), 7.68 (2H, d, J=8.8 Hz), 8.03 (1H, s), 8.25 (2H, d, J=8.8 Hz), 8.31 (1H, s).

b) Sodium (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-isopropylthioimidazo[5,1-b]thiazol-2-yl)-1-methyl-1carbapen-2-em-3-carboxylate

The title compound (85.1 mg) was obtained from 163 mg of 4-nitrobenzyl (1S,5R6S )-6-((1R)-1-hydroxyethyl)-2-(7-isopopylthioimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate in the same manner as in Example 1-b), except that the purification was, carried out by column chromatography on Cosmosil 40C18-PREP (5% aqueous methanol).

NMR (D 2 O) δ (HOD=4.80 ppm): 1.18 (6H, d, J=6.8 Hz), 1.22 (3H, d, J=7.2 Hz), 1.31 (3H, d, J=6.3 Hz), 3.21 (1H, sept, J=6.8 Hz), 3.45-3.6 (2H, m), 4.2-4.35 (2H, m), 7.86 (1H, s), 8.10 (1H, s).

›Example 159

Sodium (5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7- isopropylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2 -em-3-carboxylate

a) 4-Nitrobenzyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-isopropylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 1-a), 261 mg of 4-nitrobenzyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-isopropylthioimidazo[5,1 b]thiazol-2′yl)-1-carbapen-2-em-3-carboxylate was obtained from 348 mg of 4-nitrobenzyl (3R,5R,6S)-6-((1R)-1-hydroxyethyl)-2 oxo-1-carbapenam-3-carboxylate and 506 mg, of 7-isopropylthio-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole.

NMR (CDCl 3 ) δ: 1.27 (6H, d, J=6.7 Hz), 1.40 (3H, d, J=6.3 Hz), 3.2-3.4, (4H, m), 4.25-4.4 (2H, m), 5.32 (1H, d, J=13.7 Hz), 5.55 (1H, d, J=13.7 Hz), 7.69 (2H, d, J=8.8 Hz), 8.02 (1H, s), 8.21 (1H, s), 8.25 (2H, d, J=8.8 Hz).

b) Sodium (5R,6S)-6-((1-R)-1-hydroxyethyl)-2-(7-isopropylthioimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate

The title compound (55.1 mg) was obtained from 110 mg of 4-nitrobenzyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-isopropylthioimidazo[5,1-b]thiazol-2′-yl)-1-carbapen-2-em-3-carboxylate in the same manner as in Example 1-b), except that the purification was carried out by column chromatography on Cosmosil 40C18-PREP (5% aqueous methanol).

NMR (D 2 O) δ (HOD=4.80 ppm): 1.18 (6H, d, J=6.8 Hz), 1.31 (3H, d, J=6.5 Hz), 3.15-3.35 (3H, m), 3.49 (1H, dd, J 1 =6.0 Hz, J 2 =3.0 Hz)., 4.2-4.3 (2H, m), 7.66 (1H, s), 8.06 (1H, s).

›Example 160

1-Methylcyclohexylcarbonyloxymethyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonyl-5-methylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 2,21 mg of the title compound was obtained from21 mg of sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonyl-5-methylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate and 27 mg of 1-methylcyclohexylcarbonyloxymethyl iodide.

NMR (CDCl 3 ) δ: 1.15 (3H, s), 1.27 (3H, d, J=7.2 Hz), 1.37 (3H, d, J=6.2 Hz), 1.25-1.70 (8H, m), 1.95-2.03 (2H, m), 2.69 (3H, s), 3.19 (3H, s), 3.34 (1H, dd, J 1 =7.5 Hz, J 2 =2.8 Hz), 3.44 (1H, m), 4.29 (1H, m), 4.36 (1H, dd, J 1 =9.8 Hz, J 2 =2.8 Hz), 5.90, 5.98 (2H, ABq, J=5.6 Hz), 8.27 (1, s); MS (TSP): 580 (M + +H).

›Example 161

1-(Cyclohexyloxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonyl-5-methylimidazo[5,1-b]thiazol-2-yl)-1-ethyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example 2, 21 mg of the title compound was obtained from 23 mg of sodium (1S,5R,6-S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonyl-5-methylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate and 0.025 ml of 1-(cyclohexyloxycarbonyloxy)ethyl iodide.

NMR (CDCl 3 ) δ: 1.25-1.40 (8H, s), 1.50-1.95 (8H, m), 1.60, 1.65 (total 3H, d each, J=5.5 Hz), 2.65 (3H, s), 3.20 (3H, s), 3.34 (1H, m), 3.44 (1H, m), 3.62 (1H, m), 4.27 (1H, m) 4.35 (1H, m), 4.65 (1H, m), 6.94 (1H, m), 8.38, 8.43 (total 1H, s each); MS (TSP): 596 (M + +H).

›Example 162

Cyclohexyloxycarbonyloxymethyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonyl-5-methylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 2, 24 mg of the title compound was obtained from 20 mg of sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonyl-5-methylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate and 0.026 ml of cyclohexyloxycarbonyloxymethyl iodide.

NMR (CDCl 3 ) δ: 1.26 (3H, d, J=7.2 Hz), 1.36 (3H, d, J=6.2 Hz), 1.42-1.48 (4H, m), 1.68-1.98 (6H, m), 2.67 (3H, s), 3.20 (3H, s), 3.34 (1H, dd, J 1 =6.8 Hz, J 2 =2.9 Hz), 3.45 (1H, m), 4.30 (1H, m), 4.35 (1H, dd, J 1 =9.7 Hz, J 2 =2.9 Hz), 4.66 (1H, m), 5.88, 5.97 (2H, ABq, J=5.8 Hz), 8.37 (1H, s); MS (TSP): 582 (M + +H).

›Example 163

3-Phthalidyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonyl-5-methyl-imidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example 2, 17 mg of the title compound was obtained from 22 mg of sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonyl-5-methylimidazo[5,1-thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate and 22 mg of 3-phthalidyl bromide.

NMR (CDCl 3 ) δ: 1.26 (3H, m), 1.35 (3H, m), 2.60, 2.67 (total 3H, s each), 3.18, 3.20 (total 3H, s each), 3.35 (1H, m), 3.49 (1H, m), 4.23 (1H, m), 4.97 (1H, m), 7.45, 7.47 (total 1H, each), 7.65-7.80 (3H, m), 7.92 (1H, m), 8.14, 8.43 (total 1H, s each); MS (TSP): 558 (M + +H).

›Example 164

5-Methyl-2-oxo-1,3-Dioxolen-4-ylmethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonyl-5-methylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 2, 18 mg of the title compound was obtained from 22 mg of sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonyl-5-methylimidazo[5,1-b]thiazol-2y)-1-methyl-1carbapen-2-em-3-carboxylate and 19 mg of 5-methyl-2-oxo-1, 3-dioxolen-4-ylmethyl bromide.

NMR (CDCl 3 ) δ: 1.29 (3H, d, J=7.2 Hz), 1.37 (3H, d, J=6.3 Hz), 2.22 (3H, s), 2.66 (3H, s), 3.20 (3H, s), 3.35 (1H, dd, J 1 =6.6 Hz, J 2 =2.8 Hz), 3.48 (1H, m), 4.29 (1H, m), 4.37, (1H, dd, J 1 =9.7 Hz, J 2 =2.8 Hz), 5.02, 5.10 (2H, ABq, J=14.0 Hz), 8.18 (1H, s); MS (TSP): 538 (M + +H).

›Example 165

(Z)-2-(3-Phthalidylidene)ethyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonyl5-methylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 2, 25 mg of the title compound was obtained from 24 mg of sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonyl-5-methylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate and 26 mg of (Z)-2-(3-phthalidylidene)ethyl bromide.

NMR (CDCl 3 ) δ: 1.28 (3H, d, J=7.4 Hz), 1.37 (3H, d, J=6.2 Hz), 2.65 (3H, s), 3.19 (3H, s), 3.34 (1H, dd, J 1 =6.5 Hz, J 2 =2.7 Hz), 3.45 (1H, m), 430 (1H, m), 4.36 (1H, dd, J 1 =9.6 Hz, J 2 =2.7 Hz), 5.23 (2H, m), 5.84 (1H, m), 7.60 (1H, m), 7.72 (2H, m), 7.90 (1H, m), 8.33 (1H, s); MS (TSP): 584 (M + +H).

›Example 166

1-(Ethoxycarbonyloxy)ethyl (1S,5R,6S)-2-(7-Acetyl-5-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example 2, 24 mg of the title compound was obtained from 23 mg of sodium (1S,5R,6S)-2-(7-acetyl-5-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate and 0.030 ml of 1-(ethoxycarbonyloxy)ethyl iodide.

NMR (CDCl 3 ) δ: 1.27 (3H, m), 1.37 (6H, m), 1.60 (3H, m), 2.58 (3H, s), 2.67 (3H, s), 3.33 (1H, m), 3.48 (1H, m), 4.20-4.30 (4H, m), 4.37 (1H, m), 6.94 (1H, m), 8.44, 8.48 (total 1H, s each); MS (TSP): 506 (M + +H).

›Example 167

1-(Cyclohexyloxycarbonyloxy)ethyl (1S,5R,6S)-2-(7-Acetyl-5-methylimidazo[5,1-b]thiazol12-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example 2, 19 mg of the title compound was obtained from 23 mg of sodium (1S,5R,6S)-2-(7-acetyl-5-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate and 0.034 ml of 1-(cyclohexyloxycarbonyloxy)ethyl iodide.

NMR (CDCl 3 ) δ: 1.27 (3H, m), 1.30-1.95 (10H, m), 1.37 (3H, m), 1.65 (3H, m), 2.58 (3H, s), 2.67 (3H, s), 3.34 (1H, m), 3.50 (1H, m), 4.28 (1H, m), 4.35 (1H, m), 4.64 (1H, m), 6.94 (1H, m), 8.45, 8.48 (total 1H, s each); MS (TSP): 560 (M + +H).

›Example 168

Cyclohexyloxycarbonyloxymethyl (1S,5R,6S)-2-(7-Acetyl-5-methylimidazo[5,1b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 2, 25 mg of the title compound was obtained from 21 mg of sodium (1S,5R,6S)-2-(7-acetyl-5-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate and 29 mg of cyclohexyloxycarbonyloxymethyl iodide.

NMR:(CDCl 3 ) δ: 1.27 (3H, d, J=7.2, Hz), 1.37 (3H, d, J=6.3 Hz), 1.35-2.00 (10H, m), 2.58 (3H, s), 2.68 (3H, s), 3.34 (1H, dd, J 1 =6.5 Hz, J 2 =2.7 Hz)l 3.47 (1H, m), 4.30 (1H, m), 4.37 (1H, dd, J 1 =9.8 Hz, J 2 =2.7 Hz), 4.65 (1H, m), 5.88, 5.97 (2H, ABq, J=5.9 Hz), 8.421 (1H, s); MS (TSP): 546 (M + +H).

›Example 169

3-Phthalidyl (1S,5R,6S)-2-(7-acetyl-5-Methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example 2, 22 mg of the title compound was obtained from 20 mg of sodium (1S,5R,6S)-2-(7-acetyl-5-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate and 22 mg of 3-phthalidyl bromide.

NMR (CDCl 3 ) δ: 1.28 (3H, m), 1.33 (3H, m), 2.12 (1H, m), 2.57, 2.59 (total 3H, s each), 2.64, 2.69 (total 3H, s each), 3.36 (1H, m), 3.51 (1H, m), 4.24 (1H, m), 4.37 (1H, m), 7.46, 7.48 (total 1H, s each), 7.23-7.70 (3H, m), 7.93 (1H, m), 8.25, 8.54 (total 1H, s each). MS (TSP): 522 (M 4 +H).

›Example 170

5-Methyl-2-oxo-1, 3-Dioxolen-4-ylmethyl (1S,5R,6S)-2(7-acetyl-5-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 2, 26 mg of the title compound was obtained from 22 mg of sodium (1S,5R,6S)-2-(7-acetyl-5-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate and 20 mg of 5-methyl-2-oxo-1, 3-dioxolen-4-ylmethyl bromide.

NMR (CDCl 3 ) δ: 1.29 (3H, d, J=7.1 Hz), 1.38 (3H, d, J=6.3 Hz), 1.91 (1H, br·m), 2.22 (3H, s), 2.58 (3H, s), 2.68 (3H, s), 3.35 (1H, dd, J 1 =6.5 Hz, J 2 =2.7 Hz), 3.50 (1H, m), 4.30 (1H, m), 4.37 (1H, dd, J 1 =9.5 Hz, J 2 =2.7 Hz), 4.99, 5.09 (2H, ABq, J=13.7 Hz), 8.26 (1H, s). MS (TSP): 502 (M + +H).

›Example 171

Cyclopentyloxycarbonyloxymethyl (1S,5R,6S)-2-(7-Acetyl-5-methylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1 i-2-em-3-carboxylate

In the same manner as in Example 2, 28 mg of the title compound, was obtained from 23 mg of sodium (1S,5R,6S)-2-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate and 30 mg of cyclopentyloxycarbonyloxymethyl iodide.

NMR (CDCl 3 ) δ: 1.28 (3H, d, J=7.2 Hz), 1.37 (3H, d, J=6.3 Hz), 1.60-1.95 (8H, m), 2.58 (3H, s), 2.68 (3H, s), 3.40 (1H, dd, J 1 =6.6 Hz, J 2 =2.8 Hz), 3.49 (1H, m), 4.30 ((1H, m), 4.39 (1H, dd, J 1 =9.9 Hz, J 2 =2.8 Hz), 5.12 (1H, m), 5.87, 5.96 (2H, ABq, J=5.8 Hz), 8.43 (1H, s); MS (TSP): 532 (M + +H).

›Example 172

1-(Pivaloyloxy)ethyl (1S,5R,6S)-2-(7Acetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-methyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example 2, 331 mg of the title compound was obtained from 396 mg of sodium (1S,5R,6S)-2-(7-acetylimidazo[5, 1-b]thiazol-2-yl), -6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate and 495 mg of 1-(pivaloyloxy)ethyl iodide.

NMR (CDCl 3 ) δ: 1.11, 1.17 (total 9H, s each), 1.22 (3H, m), 1.34 (3H, m), 1.50, 1.55 (total 3H, d each, J=5.5 Hz), 2.56 (3H, s), 3.32 (1H, m), 3.45 (1H, m), 4.24 (1H, m), 4.37 (1H, m), 6.98 (1H, m), 8.0.1 (1H, s), 8.49, 8.51 (total 1H, s each); MS (TSP): 504 (M + +H).

›Example 173

1-Methylcyclohexylcarbonyloxymethyl (1S,5R,6S)-2-(7-Acetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 2, 301 mg of the title compound was obtained from 229 mg of sodium (1S,5R,6S)-2-(7-acetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate and 253 mg of 1-methylcyclohexylcarbonyloxymethyl iodide.

NMR (CDCl 3 )δ: 0.90-1.54 (8H, m), 120 (3H, s), 1.27 (3H, d, J=7.4 Hz), 1.35 (3H, d, J=6.1 Hz), 1.95-2.01 (2H, m), 2.60 (3H, s), 3.35 (1H, dd, J 1 =6.5 Hz, J 2 =2.7 Hz), 3.49 (1H, m), 4.28 (1H, m), 4.39 (1H, dd, J 1 =9.7 Hz, J 2 =2.7 Hz), 5.89, 5.96 (2H, ABq, J=5.5 Hz), 8.05 (1H, s), 8.48 (1H, s); MS (TSP): 530 (M + +H).

›Example 174

Cyclohexylcarbonyloxymethyl (1S,5R,6S)-2-(7-Acetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 2, 288 mg of the title compound was obtained from 228 mg of sodium (1S,5R,6S)-2-(7-acetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate and 236 mg of cyclohexylcarbonyloxymethyl iodide.

NMR (CDCl 3 ) δ: 1.15-1.75 (8H, m), 1.28 (3H, d, J=7.1 Hz), 1.37 (3H, d, J=6.0 Hz), 1.80-1.95 (2H, m), 2.35 (1H, m), 2.62 (3H, s), 3.35 (1H, dd, J 1 =6.5 Hz, J 2 =2.8 Hz), 3.49 (1H, m), 4.30 (1H, m), 4.39 (1H, dd, J, 9.6 Hz, J 2 =2:8 Hz), 5.88, 5.96 (2H, ABq, J=5.8 Hz), 8.05 (1H, s), 8.51 (1H, s); MS (TSP): 516 (M + +H).

›Example 175

1-(Cyclohexylcarbonyloxy)ethyl (1S,5R,6S)-2-(7-Acetylimidazo[5,1-b]thiazol-2-yl)-6-((i1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example 2, 286 mg of the title compound was obtained from 290 mg of sodium (1S,5R,6S)-2′-(7-acetylimidazo[5,1-b]thiazol-2-yl)- 6 -((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate and 338 mg of 1-(cyclohexylcarbonyloxy)ethyl iodide.

NMR (CDCl 3 ) δ: 1.25 (3H, m), 1.20-1.95 (8H, m), 1.36 (3H, m), 1.53, 1.58 (total 3H, d each, J=5.5 Hz), 2.25-2.38 (3H, s), 3.10 (3H, s), 3.34 (1H, m), 3.46 (1H, m), 4.27 (1H, m), 4.39 (1H, m), 7.01 (1H, m), 8.05 (1H, s), 8.30, 8.57 (total 1H, s each); MS (TSP): 530 (M + +H).

›Example 176

Hexanoyloxymethyl (1S,5R,6S)-2-(7-Acetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 2, 95.3 mg of the title compound was obtained from 94 mg of sodium (1S,5R,6S)-2-(7-acetylimidazo[5,1-b]thiazol2-yl)-6((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate and 109 mg of hexanoyloxymethyl iodide.

NMR (CDCl 3 ) δ: 0.87 (3H, t, J=6.7 Hz), 1.2-1.35 (7H, m), 1.38 (3H, d, J=6.3 Hz), 1.55-1.7 (2H, m), 2.37 (2H, t, J=7.7 Hz), 2.62 (3H, s), 31.36 (1H, dd, J 1 =6.6 Hz, J 2 =2.8 Hz), 3.45-3.6 (1H, m), 4.25-4.35 (1H, m), 4.39 (1H, dd, J 1 =9.8 Hz, J 2 =2.8 Hz), 5.90 (1H, d, J=5.7 Hz), 5.97 (1H, d, J=5.7 Hz), 8.04 (1H, s), 8.54 (1H, s); MS (TSP): 504 (M + +H).

›Example 177

2-Ethylbutyryloxymethyl (1S,5R,6S)-2-(7-Acetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 2, 229 mg of the title compound was obtained from 265 mg of sodium (1S,5R,6S)-2-(7-acetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate and 390 mg of 2-ethylbutyryloxymethyl iodide.

NMR (CDCl 3 ) δ: 0.8-0.9 (6H, m), 1.28 (3H, d, J=7.4 Hz), 1.36 (3H, d, J=6.3 Hz), 1.45-1.7 (4H, m), 2.2-2.3 (1H, m), 2.62 (3H, 1S), 3.36 (1H, dd, J 1 =6.8, Hz, 2 2.9 Hz), 3.45-3.55 (1H, m), 4.25-4.35 (1H, m), 4.39 (1H, dd, J 1 =9.8 Hz, J 2 =2.9 Hz), 5.95 (2H, s), 8.05 (1H, s), 8.52 (1H, s); MS (TSP): 504 (M + +H).

›Example 178

Cyclopentyloxycarbonyloxymethyl (1S,5R,6S)-2-(7-Acetylimidazo[5,1-b]thiazol-2-yl )-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 2, 297 mg of the title compound was obtained from 235 mg of sodium (1S,5R,6S)-2-(7-acetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate and 249 mg of cyclopentyloxycarbonyloxymethyl iodide.

NMR (CDCl 3 ) δ: 1.27 (3H, d, J=7.1 Hz), 1.35 (3H, d, J=6.1 Hz), 1.55-1.85 (8H, m), 2.60 (3H, s), 3.35 (1H, dd, J 1 =6.3 Hz, J 2 =2.5 Hz), 3.49 (1H, m), 4.29 (1H, m), 4.39 (1H dd, J 1 =9.7 Hz, J 2 =2.5 Hz), 5.10, (1H, m), 5.87, 5.94 (2H, ABq, J=5.8 Hz); 8.04 (1H, s), 8.55 (1H, s); MS (TSP): 518 (M + +H).

Example179

1-(3-Pentyloxycarbonyloxy)ethyl (1S,5R,6S)-2-(7-Acetylimidazo[5,1-b]thiazol-2-yl)-64((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3′carboxylate (a Mixture of Diastereomers)

In the same manner as in Example 2; 243 mg of the title compound was obtained from 246 mg of sodium (1S,5R,6S)-2-(7-acetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate and 300 mg of 1-(3-pentyloxycarbonyloxy)ethyl iodide.

NMR(CDCl 3 ) δ: 0.82-0.95 (6H, m), 1.26 (3H, m), 1.36 (3H, m), 1.55-1.66 (7H, m), 2.61 (3H, s), 3.34 (1H, m), 3.48 (1H, m), 4.31 (1H, m), 4.35 (1H, m), 4.58 (1H, m), 6.93 (1H, m), 8.01 (1H, s), 8.58, 8.62:(total i1H, s each); MS (TSP): 534 (M + +H).

›Example 180

3-Pentyloxycarbonyloxymethyl (1S,5R,6S)-2-(7-Acetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 2, 265 mg of the title compound was obtained from 218 mg of sodium (1S,5R,6S)-2-(7-acetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate and 309 mg of 3-pentyloxycarbonyloxymethyl iodide.

NMR (CDCl 3 ) δ: 0.84 (6H, m), 1.25 (3H, d, J=7.4 Hz), 1.33 (3H, d, J=6.3 Hz), 1.56 (4H, m), 2.57 (3H, s), 3.33 (1H, dd, J 1 =6.8 Hz, J 2 =2.7 Hz), 3.47 (1H, m), 4.25 (1H, m), 4.37 (1H, dd, J 1 =9.6 Hz, J 2 =2.7 Hz), 4, 56 (1H, m), 5.87, 5.93 (2H, ABq, J=5.8 Hz), 8.03 (1H, s), 8.52 (1H, s); MS (TSP): 520 (M + +H).

›Example 181

Cyclohexylmethoxycarbonyloxymethyl (1S,5R,6S)-2-(7-Acetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 2, 317 mg of the title compound was obtained from 237 mg of sodium (1S,5R,6S)-2-(7-acetylimidazo[5,1-b]thiazol-2-yl)-1-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate and 369 mg of cyclohexylmethoxycarbonyloxymethyl iodide.

NMR (CDCl 3 ) δ: 0.90-1.30 (4H, m), 1.28 (3H, d, J=7.1 Hz) 1. 37 (3H, d, J=6.2 Hz), 1.65-1.75 (6H, m), 2.15 (1H, br·s), 2.62 (3H, s), 3.36 (1H, dd, J 1 =6.4 Hz, J 2 =2.8 Hz), 3.50 (1H, m), 3.98 (2H, d, J=6.3 Hz), 4.30 (1H, m), 4.39 (1H, dd, J 1 =9.6 Hz, J 2 =2.8 Hz), 5.90, 5.96 (2H, ABq, J 1 =5.8 Hz), 8.03 (1H, s), 8.57 (1H, 5); MS (TSP): 546 (M + +H).

›Example 182

1-(Isobutyryloxy)ethyl (1S,5R,6S)-6-((1R)-1-Hydro -2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example 2, 198 mg of the title compound was obtained from 289 mg of sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate and 323 mg of 1-(isobutyryloxy)ethyl iodide.

NMR (CDCl 3 ) δ: 1.14 (3H, m), 1.19 (3H, m), 1.26 (3H, m), 1.36 (3H, m), 1.55,1.60 (total 3H, d each, J=5.5 Hz), 2.32 (1H, br·s), 2.68 (1H, m), 3.21 (3H, s), 3.33 (1H, m), 3.46 (1H, m), 4.27 (1H, m) 4.35 (1H, m), 7.03 (1H, m), 8.09 (1H, s), 8.51, 8.53 (total 1H, s each); MS (TSP): 526 (M + +H).

›Example 183

1-(Pivaloyloxy)ethyl 1(S,5R,6S)-6-((1R)-1Hydroxyethyl)-2-(7-methanesulfonylimiidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example 2, 234 mg of the title compound was obtained from 361 mg of sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen2-em-3-carboxylate and 430 mg of 1-(pivaloyloxy)ethyl iodide.

NMR (CDCl 3 ) δ: 1.52, 1.21 (total 9H, s each), 1.25 (3H, m), 1.35 (3H, m), 1.53, 1.58 (total 3H, d each, J=3.6 Hz), 3.19 (3H, s), 3.33 (1H, m), 3.46 (1H, m), 4.25 (1H, m), 4.34 (1H, m), 7.00 (1H, m), 8.10 (1H, s), 8.46, 8.49 (total 1H, s each); MS (TSP): 540 (M + +H).

›Example 184

Hexanoyloxymethyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 2, 217 mg of the title compound was obtained from 214 mg of sodium (1S,5R,6S)-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate and 265 mg of hexanoyloxymethyl iodide.

NMR (CDCl 3 ) δ: 0.87 (3H, t, J=7.0 Hz), 1.2-1.3 (7H, m), 1.37′(3H, d, J=6.3 Hz), 155-1.7 (2H, m), 2.38 (2H, t, J=7.7 Hz), 3.24 (3H, s), 3.35 (1H, dd, J 1 =6.6 Hz, J 2 =2.7 Hz), 3.4-3.55 (1H, m), 4.25-4.35 (2H, m), 4.37 (1H, dd, J 1 =9.8 Hz, J 2 =2.7 Hz), 5.8.9 (1H, d, J=5.6 Hz), 5.96 (1H, d, J=5.6 Hz), 8.19 (1H, s), 8.49 (1H, s); MS (TSP): 540 (M + +H).

›Example 185

Cyclohexylcarbonyloxymethyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonyl-imidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 2, 267 mg of the title compound was obtained from 219 mg of sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate and 200 mg of cyclohexylcarbonyloxymethyl iodide.

NMR (CDCl 3 ) δ: 1.18-1.50 (4H, m)-1.27 (3H, d, J=7.2 Hz), 1.35 (3H, d, J=6.3 Hz), 1. 60-1.98 (6H, m), 2.35 (1H, m), 3.22 (3H, s), 3.34 (1H, dd, J 1 =6.6 Hz, J 2 =2.8 Hz), 3.47 (1H, m), 4.28 (1H, m), 4.36 (1H, dd, J 1 =9.7 Hz, J 2 =2.88 Hz), 5.88, 5.95 (2H, ABq, J=5.7 Hz), 8.12 (1H, s), 8.45 (1H, s); MS (TSP): 552 (M + +H).

›Example 186

Cyclohexylacetoxymethyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-1ethyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 2, 272 mg of the title compound was obtained from 212 mg of sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1methyl-1-carbapen-2-em-3-carboxylate and 276 mg of cyclohexylacetoxymethyl iodide.

NMR (CDCl 3 ) δ: 0.87-1.25 (6H, m), 1.25 (3H, d, J=7.2 Hz), 1.34 (3H, d, J=6.3 Hz), 1.60-1.80 (5H, m), 2.24 (2H, d, J 1 =6.9 Hz), 3.21 (3H, s), 3.33 (1H, dd, J 1 =6.7 Hz, J 2 =2.8 Hz), 3.47 (1H, m), 4.26 (1H, m), 4.34 (1H, dd, J 1 =9.6 Hz, J 2 2.8 Hz), 5.88, 5.93 (2H, ABq, J=4.3 Hz), 8.12 (1H, s), 8.44 (1H, s); MS (TSP): 566 (M + +H).

›Example 187

Dicyclohexylacetoxymethyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonyl-imidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 2, 292 mg of the title compound was obtained from 217 mg of sodium (1S,5R,6S)-7l6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate and 274 mg of dicyclohexylacetoxymethyl iodide.

NMR (CDCl 3 ) δ: 0.79-1.22 (10H, m) 1.26 (3H, d, J=7.1 Hz), 1.37 (3H, d, J=6.3 Hz), 1.60 (12H, m), 2.11 (1H, t, J=7.5 Hz), 2.57 (1H, br s), 3.22 (3H, s), 3.34 (1H, dd, J 1 =7.0 Hz, J 2 =2.9 Hz), 3.47 (1H, m), 4.25 (1H, br t), 4.33 (1H, dd, J 1 =9.8 Hz, J 2 =3.0 Hz), 5.89 (1H, d, J=5.6 Hz), 5.96 (1H, d, J=5.6 Hz), 8.15 (1H, s), 8.47 (1H, s); MS (TSP): 648 (M + +H).

›Example 188

1-(1-Methylcyclohexylcarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example 2, 287 mg of the title compound was obtained from 747 mg of sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate and 3.2 g of 1-[(1-methylcyclohexan-1-yl)carbonyloxy]ethyl iodide.

NMR(CDCl 3 ) δ: 1.12, 1.21 (total 3H, s each), 1.56, 1.62 (total 3H, d each, J=5.5 Hz), 1.1-2.1 (16H, m), 3.22 (3H, s), 3.3-3.4 (1H, m), 3.35-3.5 (1H, m), 4.2-4.35 (1H, m), 4.37 (1H, dd, J 1 =9.6 Hz, J 2 =2.7 Hz), 7.0-7.1 (1H, m), 8.09 (1H, s), M51, 8.57 (total 1H, s each); MS (TSP): 580 (M + +H).

›Example 189

1-Adamantylcarbonyloxymethyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonyl-imidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 2, 258 mg of the title compound was obtained from 217 mg of sodium (1S,5R,6S)-6-((1R) 1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate and 260 mg of 1-adamantylcarbonyloxymethyl iodide.

NMR (CDCl 3 ) δ: 1.28 (3H, d, J=7.3 Hz), 1.37 (3H, d, J 1 =6.1 Hz), 1.69 (6H, m), 1.86 (6H, m), 2.00 (3H, m), 3.22 (3H, s), 3.35 (1H, dd, J 1 =36.6 Hz, J 2 =3.0 Hz), 3.46 (1H, m), 4.29 (1H, m), 4.37 (1H, dd, J 1 =9.7 Hz, J 2 =2.9 Hz), 5.88 (1H, d, J=5.6 Hz), 5.96 (1H, d, J=5.6 Hz), 8.11 (1H, s), 18.44 (1H, s); MS (TSP): 604 (M + +H).

›Example 190

1-(1-Adamantylcarbonyloxy)ethyl (1S,5R,6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonyl-imidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example 2, 71 mg of the title compound was obtained from 184 mg of sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate and 500 mg of 1-(1-adamantylcarbonyloxy)ethyl iodide.

NMR (CDCl 3 ) δ: 1.27 (3H, m), 1.38′(3H, m), 1.55,1.60 (total 3H, d each, J=5.5 Hz), 1.62-2.07 (15H, m), 3.22 (3H, s), 3.34 (1H, m), 3.44 (1H, m), 4.29 (1H, m), 4.37 (1H, m), 7.02 (1H, m), 8.08 (1H, s), 8.53, 8.56 (total 1H, s each); MS (TSP): 618 (M + +H).

›Example 191

1-(Benzoyloxy)ethyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example 2, 147 mg of the title compound was obtained from 197 mg of sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate and 250 mg of 1-(benzoyloxy)ethyl iodide.

NMR(CDCl 3 ) δ: 1.28 (3H, m), 1.33, 1.38 (total3H, d each, J=6.2 Hz), 1.71, 1.76 (total 3H, d each, J=5.5 Hz), 3.21 (3H, s) 3.35 (3H, m), 3.44 (1H, m), 4.28 (1H, m), 4.37 (1H, m), 7.30 ′(1H, m), 7.45 (2H, m), 7.60 (1H, m), 8.00, 8.02 (total 1H, s each); 8.07 (2H, m), 8.51, 8.57 (total 1H, s each); MS (TSP): 560 (M + +H).

›Example 192

4-(2-Propyl)benzoyloxymethyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonyl-imidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 2, 102 mg of the title compound was obtained from 92 mg of sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate and 120 mg of 4-(2-propyl)benzoyloxymethyl iodide.

NMR(CDCl 3 ) δ: 1.24 (3H, s), 1.25 (3H, d, J=7.1 Hz), 1.26 (3H, s), 1.35 (3H, d, J=6.2 Hz), 2.96 (1H, m), 3.21 (3H, s), 3.34 (1H, dd, J 1 =6.7 Hz, J 2 2.8 Hz), 3.45 (1H, m), 4.28 (1H, m), 4.36 (1H, dd, J 1 =9.6 Hz, J 2 =2.8 Hz), 6.14, 6.18 (2H, ABq, J=5.6 Hz), 7.30 (2H, d, J=8.3 Hz), 7.98 (2H, d, J=8.3 Hz), 8.09 (1H, s), 8.47 (1H, s); MS (TSP): 588 (M + +H).

›Example 193

4-n-Butylbenzoyloxymethyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonyl-imidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 2, 140 mg of the title compound was obtained from 112 mg of sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate and 180 mg of 4-n-butylbenzoyloxymethyl iodide.

NMR (CDCl 3 ) δ: 0.92 (3H, t, J=7.3 Hz), 1.26 (3H, d, J=7.4 Hz), 1.34 (2H, m), 1.35(3H, d, J=6.3 Hz), 1.60 (2H, m), 2.66 (2H, t, J=8.0 Hz), 3.21 (3H, s), 3.34 (1H, dd, J 1 =6.5 Hz, J 2 =2.9 Hz), 3.45 (1H, m), 4.28 (1H, m), 4.36 (1H, dd, J 1 =9.8 Hz, J 2 =2.9 Hz) 6.14, 6.17 (2H, ABq, J=5.6 Hz), 7.25 (2H, d, J=8.3 Hz), 7.97 (2H, d, J=8.3 Hz), 8.09 (1H, s), 8.47 (1H, s); MS (TSP): 602 (M + +H).

›Example 194

4-Phenylbenzoyloxymethyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 2, 169 mg of the title compound was obtained from 110 mg of sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-12-em-3-carboxylate and 170 mg of 4-phenylbenzoyloxymethyl iodide.

NMR (CDCl 3 ) δ: 1.27 (3H, d, J=7.3 Hz), 1.36 (3H, d, J=6.3 Hz), 2.17 (1H, br·s), 3.21 (3H, s), 3.35 (1H, dd, J=6.6 Hz, J 2 =2.8 Hz), 3.46 (1H, m), 4.29 (1H, m), 4.37 (1H, dd, J 1 =9.8 Hz, J 2 =2.8 Hz), 6.20 (2H, s), 7.45 (3H, m), 7.65 (4H, m), (1H, s), 8.13 (2H, m), 8.49 (1H, s); MS (TSP) 622 (M +H).

›Example 195

4-t-Butylbenzoyloxymethyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonyl-imidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 2, 262 mg of the title compound was obtained from 217 mg of sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate and 318 mg of 4-t-butylbenzoyloxymethyl iodide.

NMR (CDCl 3 ) δ: 1.25 (3H, d, J=7.3, Hz), 1.31 (9H, s), 1.34 (3H d, J=6.4 Hz), 3.20 (3H, s), 13.34 (1H, dd, J 1 =6.7 Hz, J 2 =2.8 Hz), 3.48 (1H, dq, J 1 =9.8 Hz, J 2 =7.3 Hz), 4.26 (1H, dq, J=6.3 Hz), 4.35 1 (1H, J 1 =9.7 Hz, J 2 =2.9 Hz), 16.14 (1H, d, J=5.6 Hz), 6.17 (1H, d, J=5.6 Hz), 7.45 (2H, m), 7.97 (2H, m), 8.12 (1H, s), 8.44 (1H, s); MS (TSP): 619 (M + +H).

›Example 196

1-(4-t-Butylbenzoyloxy)ethyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonyl-imidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-1-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example 2, 154 mg of the title compound was obtained from 192 mg of sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen- 2 -em-3-carboxylate and 300′mg of 1-(4-t-butylbenzoyloxy)ethyl iodide.

NMR(CDCl 3 ) δ: 1.26 (3H, m), 1.32, 1.34 (total 9H, s each), 1.37 (3H, m), 1.70, 1.74 (total 3H, d each, J=5.4 Hz), 3.20 (3H, s), 3.34 (1H, m), 3.44 (1H, m), 4.28 (1H, m), 4.36 (1H, m), 7.29 (1H, m), 7.46 (2H, m), 7.98 (2, H, m), 8.01 (1H, s), 8.51, 8.57 (total 1H, s each); MS (TSP): 616 (M + +H).

›Example 197

2,4,6-Trimethylbenzoyloxymethyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonyl-imidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 2, 214 mg of the title compound was obtained from 178 mg of sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate and 254 mg of 2,4,6-trimethylbenzoyloxymethyl iodide.

NMR (CDCl 3 )δ: 1.26 (3H, d, J=7.1 Hz), 1.36 (3H, d, J=6.0 Hz), 2.27 (9H, s), 3.21 (3H, s), 3.34 (1H, dd, J 1 =6.6 Hz, J 2 =2.2 Hz), 3.47 (1H, m), 4.27 (1H, m), 4.34 (1H, dd, J 1 =9.8 Hz, J 2 =2.2 Hz), 6.11, 6.15 (2H, ABq, J=5.6 Hz), 6.83 (2H, s), 8.10 (1H, s), 8.49 (1H, s). MS (TSP): 588 (M + +H.

›Example 198

1-(2-Propyloxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonyl-imidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example 12, 257 mg of the title compound was obtained from 267 mg of sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate and 300 mg of 1-(2-propyloxycarbonyloxy)ethyl iodide.

NMR (CDCl 3 ) δ: 1.28 (6H, m) 1.36 (6H, m), 1.58, 1.64 (total 3H, d each, J=5.4 Hz), 3.22 (13H, s), 3.33 (1H, m), 3.45 (1H, m), 4.28 (1H, m), 4.35 (1H, m), 4.91 (1H, m), 6.93 (1H, m), 8.09 (1H, s), 8.54 (1H, s); MS (TSP): 542 (M + +H).

›Example 199

1-(2-Butyloxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonyl-imidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example 2, 164 mg of the title compound was obtained from 220 mg of sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2 em3-carboxylate and 320 mg of 1-(2-butyloxycarbonyloxy)ethyl iodide.

NMR (CDCl 3 ) δ: 0.85-1.0 (3H, m), 1.25-1.40 (9H, m), 1.55-1.75 (6H, m), 3.22 (3H, sx2), 3.34 (1H, dd, J 1 =6.8 Hz, J 2 =2.9 Hz), 3.46 4.27 (1H, m), 4.35 (1H, m), 4.65-4.85 (1H, m), 6.94 (1H, m), 8.09 (1H, sx2), 8.55 (1H, m).

›Example 200

1-(3-Pentyloxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonyl-imidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example 2, 276 mg of the title compound was obtained from 151 mg of sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate and 199 mg of 1-(3-pentyloxycarbonyloxy)ethyl iodide.

NMR (CDCl 3 ) δ: 0.83-0.95 (6H, m) 1.23 (3H, m), 1.55, 1.70 (7H, m), 3.18 (3H, s), 3.30 (1H, m), 3.46 (1H, m), 4.22 (1H, m), 4.32 (1H, m), 4.58 (1H, m), 6.89 (1H, m), 8.10 (1H, s), 8.45, 8.47(total 1H, s each); MS (TSP):570 (M + +H).

›Example 201

1-(1-Butyloxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonyl-imidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example 2, 51.0 mg of the title compound was obtained from 200.0 mg of sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2 (7-methanesulfonylimidazo[5,1-b]thiazol-j2-yl)-1-methyl-1-carbapen72-em-3-carboxylate and 236.2 mg of 1-(1-butyloxycarbonyloxy)ethyl iodide.

NMR (CDCl 3 ) δ: 0.93 (3H, td, J 1 =7.3 Hz, J 2 =12.6 Hz), 1.26 (3H, dd, J 1 =7.3 Hz, J 2 =2.9 Hz), 1.33 (3H, dd, J 1 =6.1 Hz, J 2 =2.5 Hz), 1.55 (2H, m), 1.60 (3H, m), 1.65 (2H, m), 3.22 (3H, s), 3.35 (1H, m), 3.45 (1H, m), 4.15, 4.22(total 2H, t each, J=6.5), 4.29 (1H, m), 4.38 (1H, td, J 1 =2.6 Hz, J 2 9.8 Hz), 6.94 (1H, m), 8.06, 8.08 (total 1H, s each), 8.58, 8.59 (total 1H, s each); MS (TSP): 556 (M + +H).

›Example 202

4-Heptyloxycarbonyloxymethyl 1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonyl-imidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 2, 229 mg of the title compound was obtained from 168 mg of sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2 yl)-1-methyl-1-carbapen-2-em-3-carboxylate and 200 mg of 4-heptyloxycarbonyloxymethyl iodide.

NMR (CDCl 3 ) δ: 0.89 (6H, m), 1.26 (3H, d, J=7.2 Hz), 1.30-1.40 (4H, m), 1.35 (3H, d, J=6, 1.3 Hz), 1.56 (4H, m), 3.21 (3H, s), 3.33 (1H, dd, J 1 =6.9 Hz, J 2 =2.9 Hz), 3.47 (1H, m), 4.26 (1H, m), 435 (1H, dd, J 1 =9.8 Hz, J 2 =2.9 Hz), 4.74 (1H, m), 5.89, 5.95 (2H, ABq, J=5.8 Hz), 8.11 (1H, s), 8.50 (1H, s); MS (TSP):584 (M + +H).

›Example 203

1-(4-Heptyloxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonyl-imidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers).

In the same manner as in Example 2, 171 mg of the title compound was obtained from 178 mg of sodium (1S,5R,6S)-6-((1R)-l1-hydroxyethyl)-2-(7-methane sulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate and 300 mg: of 1-(4-heptyloxycarbonyloxy)ethyl iodide.

NMR (CDCl 3 ) δ 0.90 (6H, m), 1.28 (3H, m), 1.38 (3H, m), 1.30-1.65 (8H, m), 1.60, 1.66 (total 3H, d each, J=5.3 Hz), 3.22 (3H, s), 3.34 (1H, m), 3.45 (1H, m), 4.27 (1H, m), 4.35 (1H, m), 4.75 (1H, m), 6.93 (1H, m), 8.07 (1H, s), 8.56, 8.60 (total 1H, s each); MS (TSP):598 (M + +H).

›Example 204

1-(1-Pentyloxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonyl imidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example 2, 235 mg of the title compound was obtained from 220 mg of sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate and 300 mg of 1-(1-pentyloxycarbonyloxy)ethyl iodide.

NMR (CDCl 3 ) δ: 0.86-0.92 (3H, m), 1.27, 1.37 (total 3H, d each, J=7.5 Hz), 1.37, 1.38 (total 3H, d each, J=6.5 Hz), 1.60, 1.65 (total 3H, d each, J=5.4 Hz), 1.60-1.80 (2H, m), 2.00 (1H, br·s), 3.22 (3H, s) 3.40-3.50 (1H, qx2), 4.10-4.38 (4H, m), 6.94 (1H, d, J=5.4 Hz), 8.80 (1H, s), 8.57 (1H, s)

›Example 205

1-(4-Methyl-1-Pentyloxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example 2 the title compound was obtained from 220 mg of sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methane-sulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate and 320 mg of 1-(4-methyl-1-pentyloxycarbonyloxy)ethyl iodide.

NMR (CDCl 3 ) δ: 0.86, 0.89 (total 3H, d, J=6.6 Hz), 1.29 (3H, d, J=7.3 Hz), 1.20-1.30 (2H, m), 1.38, 1.39 (total 13H, d, a 6.3 Hz), 1.60, 1.66 (total 3H, d, J=5.4 Hz), 1.50-1.70 (2H, m), 1.95 (1H, dd, J 1 =8.5 Hz, J 2 =4.7 Hz), 3.22 (3H, s), 3.34 (1H, dd, J 1 =6.3 Hz, J 2 =2.7 Hz), 3.45 (1H, dq, J 1 =9.3 Hz, J 2 =7.3 Hz), 4.08-4.40 (4H, m), 6.94 (1H, q, J=5.4 Hz), 8.80 (1H, s), 8.56, 8.57 (1H, s).

›Example 206

5Nonyloxycarbonyloxymethyl (1S,5R,6S)-6-((1R))-1-Hydroxyethyl)-2-(7-methanesulfonyl-imidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 2, 218 mg of the title compound was obtained from 184 mg of sodium (1S,5R,6S)-6-((1R) 1-hydroxyethyl)-2-(7-methane-sulfonylimidazo[5,1-b]thiazol-2-yl) 1methyl-1-carbapen-2-em-3-carboxylate and 250 mg of 5-nonyloxycarbonyloxymethyl iodide.

NMR (CDCl 3 ) δ: 0.88 (6H, m)i, 1.28 (3H, d, J=7.2 Hz), 1.33 (8H, m), 1.37 (3H, d, J=6.3 Hz), 1.58 (4H, m), 3.22 (3H, s), 3.35 (1H, dd, J 1 =6.8 Hz, J 2 =2.7 Hz), 3.47 (1H, m), 4.28 (1H, m), 4.37 (1H, dd, J 1 =9.7 Hz, J 2 =2.7 Hz), 4.73 (1H, m), 5.91, 5.97 (2H, ABq, J 1 =5.8 Hz), 8.09 (1H, s), 8.54 (1H, s); MS (TSP):612 (M + +H).

›Example 207

1-(5-Nonyloxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers).

In the same manner as in Example 2, 171 mg of, the title compound was obtained from 192 mg of sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methane sulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate and 600 mg of 1-(5-nonyloxycarbonyloxy)ethyl iodide.

NMR (CDCl 3 ) δ: 0.88 (6H, m), 1.26-1.38 (14H, m), 1.58-1.70 (7H, m), 3.21 (3H, s), 3.33 (1H, m), 3.45 (1H, m), 4.25 (1H, m), 4.33 (1H, m), 4.71 (1H, m), 6.93 (1H, m), 8.07 (1H, s), 8.55, 8.58 (total 1H, s each); MS (TSP):626 (M + +H).

›Example 208

1-(2, 2-Dimethyl-1-Propyloxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example 2, 80.9 mg of the title compound was obtained from sodium 1(1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methane-sulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate and 240.8 mg of 1-(2, 2-dimethyl-1-propyloxycarbonyloxy)ethyl iodide.

NMR (CDCl 3 ) δ: 0.94, 0.98 (total 9H, s each), 1.27, 1.29 (total 3H, d each, J=3.9 Hz), 1.35,1.3:8 (total 3H, d each, J=6.3 Hz), 1.61, 1.67 (total 3H, d each, J=5.6 Hz), 3.22 (3H, s), 3.34 (1H, m), 3.45 (1H, m), 3.88 (2H, m), 4.28 (1H, q, J=6.6 Hz), 4.36 (1H, td, J 1 =2.5 Hz, J 2 =10.0 Hz), 6.93, 6.95 (total 1H, q each, J=5.6 Hz), 8.07, 8.07 (total 1H, s each), 8.55, 8.57 (total 1H, s each); MS (TSP) 570 (M + +H).

›Example 209

1-(3,3-Dimethyl-2-Butyloxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers).

In the same manner as in Example 2, 124.1 mg of the title compound was obtained from 200.0 mg of sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2 (7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate and 207.8 mg of 1-(3, 3-dimethyl-2-butyloxycarbonyloxy)ethyl iodide.

NMR (CDCl 3 ) δ: 0.88, 0.91, 0.94, 0.96(total9H, s each), 1.27, 1.29 (total 3H, d each, J=7.0 Hz), 1.36, 1.38 (total 3H, d each, J=6.3 Hz), 1.60 (3H, d, J=5.4 Hz), 1.66 (3H, d, J=5.3 Hz), 3.22 (3H, s), 3.34 (i1H, m), 3.45 (1H, m), 4.28 (1H, m), 4.36 (1H, m), 4.66 (1H, m), 6.94 (1H, m), 8.05, 8.05, 8.06, 8.07 (total 1H, s each), 8.55, 8.57, 8.59, 8.60 (total 1H, s each); MS (TSP): 584 (M + +H).

›Example 210

Cyclohexylmethoxycarbonyloxymethyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 2, 283 mg of the title compound was obtained from 218 mg of sodium (1S,5R,6S)-6-((1R) 1-hydroxyethyl)-2-(7-methane-sulfonylimidazo[5,1-b]thiazol-2 yl)-methyl-1-carbapen-1.2-em-3-carboxylate and 225 mg of cyclohexylmethoxycarbonyloxymethyl iodide.

NMR (CDCl 3 ) δ: 0.92-1.30 (6H, m), 1.26 (3H, d, J=7.2 Hz), 1.35 (3H, d, J=6.3 Hz), 1.70-1.80 (5H, m), 3.21 (3H, s), 3.33 (1H, dd, J 1 =6.7 Hz, J 2 =21.7 Hz), 3.47 (1H, m), 3.98 (3H, d, J=4.2 Hz), 4.27 (1H, m), 4.35 (1H, dd, J 1 =9.8 Hz, J 2 =2.7 Hz), 5.89, 5.94 (2H, ABq, J=5.8 Hz), 8.12 (1H, s), 8.48 (1H, s); MS (TSP):582 (M + +H).

›Example 211

1-(Cyclohexylmethoxycarbonyloxy)-1-Propyl(1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example2, 225 mg of the title compound was obtained from 414 mg of sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate 5and 2.07 g of 1-[(cyclohexylmethoxy)carbonyloxy]-1-propyl iodide.

NMR (CDCl 3 ) δ: 1.00, 1.08 (total 3H, t each, J=7.6 Hz), 1.27 (3H, d, J=7.4′Hz), 0.9-2.2 (16H, m), 3.22 (3H, s), 3.34 (1H, dd, J 1 =6.7 Hz, J 2 =2.8 Hz), 3.4-3.5 (1H, m), 3.8-4.05 (2H, m), 4.2-4.4 (2H, m), 6.78, 6.80 (total 1H, t each, J=5.5 Hz), 8.08, 8.09 (total 1H, s each), 8.57, 8.59 (total 1H, s each); MS (TSP): 610 (M + +H).

›Example 212

1-(Dicyclohexylmethoxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers).

In the same manner as in Example 2,69 mg of the title compound was obtained from 260 mg of sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methane sulfonylimidazo[5,1-b]thiazol-2-yl)- -methyl-1-carbapen-2-em-3-carboxylate and 630 mg of 1-(dicyclohexylmethoxycarbonyloxy)ethyl iodide.

NMR (CDCl 3 ) δ: 0.88-1.23 (10H, m), 1.27 (3H, d, J=7.4 Hz), 1.37 (3H, d, J=6.5 Hz), 1.57-1.7:4 (12H, m), 1.61, 1.66 (total 3H, d each, J=, 5.3 Hz), 3.21 (3H, s), 3.33 (1H, m), 3.47 (1H, m), 4.25 (1H, m), 4.34 (1H, ), 4.43 (1H, m), 6.91 (1H, m), 8.08 (total 1H, s each), 8.49, 8.56 (total 1H, s each); MS (TSP):678 (M + +H).

›Example 213

Cyclohexyloxycarbonyloxymethyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonyl-imidazo[5,1 b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 2, 191 mg of the title compound was obtained from 188 mg of sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate and 259 mg of cyclohexyloxycarbonyloxymethyl iodide.

NMR (CDCl 3 ) δ: 1.28′(3H, d, J=7.1 Hz), 1.37 (3H, d, J=6.1 Hz), 1.2-2.0 (10H, m), 3.23 (3H, s), 3.35 (1H, dd, J 1 =6.4 Hz, J 2 =2.7, Hz), 3.4-3.5 (1H, m), 4.25-4.35 (1H, m), 4.38 (1H, dd, J 1 =9.9 Hz, J 2 =2.7 Hz), 4.6-4.7 (1H, m), 5.90(1H, d, J=5. 8 Hz), 5.96 (1H, d, J=8 Hz), 8.09 (1H, s), 8 54 (1H, s); MS (TSP): 568 (M + +H).

›Example 214

1-(Cyclohexyloxycarbonyloxy)-2-methyl-1-propyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers).

In the same manner as in Example 2, 151 mg of the title compound was obtained from 268 mg of sodium (1S,5R,6S)-6(1R)hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate and 900 mg of 1-(cyclohexyloxycarbonyloxy)-2-methyl-1-propyl iodide.

NMR (CDCl 3 ) δ: 1.02 (6H, m), 1.29 (3H, m), 1.37 (3H, m), 1.31-2.20 (11H, m), 3.22 (3H, s), 3.34 (1H, m), 3.45 (1H, m), 4.28, (1H, m), 4.36 (1H, m), 4.64 (1H, m), 6.63, 6.68 (total 1H, d each, J=5,1 Hz), 8.07, 8.08 (total 1H, s each), 8.59, 8.60 (total 1H, s each); MS (TSP): 610 (M + +H).

›Example 215

Cyclohexyl (Cyclohexyloxycarbonloxy)methyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers).

In the same manner as in Example 2, 208 mg of the title compound was obtained from 275 mg of sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate and 600 mg of cyclohexyl(cyclohexyloxycarbonyloxy)methyl iodide.

NMR (CDCl 3 ) δ: 1.20-2.05 (2:1H, m), 1.28 (3H, m), 1.38 (3H, m), 3.22 (3H, s), 3.34 (1H, m), 314 (1H, m), 4.29 (1H, m), 4.36 (1H, m), 4.64 (1H, m), 6.63, 6.67 (total 1H, d each, J=5.5 Hz), 8.06 (1H, s), 8.60 (1H, s); MS (TSP): 650 (M + +H).

›Example 216

(1R,2S,5R)-(1)-Menthyloxycarbonyloxymethy (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 2, 232 mg of the title compound was obtained from 173 mg of sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate and 198 mg of (1R,2S, 5R)-(1)-menthyloxycarbonyloxymethyl iodide.

NMR (CDCl 3 ) δ: 0.76 (3H, d, J=6.9 Hz), 0.88 (6H, m), 1.00-1.50 (4H, m), 1.27 (3H, d, J=7.1 Hz), 1.36 (3H, d, J=6.3 Hz), 1.65-2.10 (4H, m), 2.35 (1H, br·s), 3.22 (3H, s) 3.33 (1H, dd, J 1 =6.9 Hz, J 2 =2.7 Hz), 3.47 (1H, m), 4.27 (1H, m), 4.34 (1H, dd, J 1 =9.8 Hz, J 2 =2.7 Hz), 4.55 (1H, m), 5.91, 5.95 (2H, ABq, J=5.7 Hz), 8.10 (1H, s), 8.52 (1H, s); MS (TSP): 624 (M + +H).

›Example 217

1-((1R,2S,5R)-(1)-Menthyloxycarbonyloxy)-ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers).

In the same manner as in Example 215 mg of the title compound was obtained from 187 mg of sodium (1S,5R,6s)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate and300mg of 1-((1R,2S,5R)-(1)-menthyloxycarbonyloxy)ethyl iodide.

NMR(CDCl 3 ) δ: 0.79 (3H, m), 0.89 (6H, m), 0.90-1.50 (4H, m), 1.27 (3H, d, J=7.1 Hz), 1.37′(3H, m), 1.60, 1.66 (total 3H, d each, J=5.5 Hz), 1.82-2.20 (4H, m), 3.22 (3H, s), 3.32 (1H, m), 3.45 (1H, m), 4.27(11H, m), 4.35 (1H, m), 4.53 (1H, m), 6.93 (1H, m), 8.07, 8.08 (total 1H, s each), 8.55, 8.59 (total 1H, s each); MS (TSP): 638 (M + +H).

›Example 218

(1S,2R,5s)-(d)-Menthyloxycarbonyloxymethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 2, 236 mg of the title compound was obtained from 164 mg of sodium (1S,5R,6s)-6-((1R-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-, 2-em-3-carboxylate and 333 mg of (1S,2R,5s)-(d)-menthyloxycarbonyloxymethyl iodide.

NMR (CDCl 3 ) δ: 0.74 (3H, d, J=6.9 Hz), 0.89 (6H, m), 1.00-1.10 (2H, m), 1.28 (3H, d, J=7.4 Hz), 1.37 (3H, d, J=6.3 Hz), 1.40-2.14 (6H, m), 3.22 (3H, s), 3.34 (1H, dd, J 1 =6.9 Hz, J 2 =2.8 Hz), 3.47 (1H, m), 4.28 (1H, m), 4.36 (1H, dd, J 1 =9.8 Hz, J 2 =28 Hz), 4.54 (1H, m), 5.88, 5.98 (2H, ABq, J=5.8 Hz), 8.10 (1H, s), 8.54 (1H, s); MS (TSP): 62.4 (M +H).

›Example 219

(1S,2R,5R)-isomenthyloxycarbonyloxymethyl 1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2′-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 2, 214 mg of the title compound was obtained from 157 mg of sodium (1S,5R,6s)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b] thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate and 291 mg of (1S,2R,5R)-isomenthyloxycarbonyloxymethyl iodide.

NMR (CDCl 3 ) δ: 0.84 (3H, d, J=6.6 Hz), 0.91 (6H, m), 1.15-1.90 (9H, m), 1.26 (3H, d, J=7.4 Hz), 1.36 (3H, d, J=6.3 Hz), 3.22 (3H, s), 3.33 (1H, dd, J 1 =6.8 Hz, J 2 =2.8 Hz), 3.47 (1H, m), 4.27 (1H, m), 4.35 (1H, dd, J 1 =9.8 Hz, J 2 =2.8 Hz), 4.91 (1H, m), 5.88, 5.97 (2H, ABq, J=5.8 Hz), 8.10 (1H, s), 8.52 (1H, s); MS (TSP): 624 (M + +H).

›Example 220

(1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-2 -(7-methanesulfonylimidazo[5,1-b]thiazol-2 yl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 2, 212 mg of the title compound was obtained from 151 mg of sodium (1S,5R,6s)-6-((1R)r -hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate and 270 mg of (1S,2S,5R) neomenthyloxycarbonyloxymethyl iodide.

NMR (CDCl 3 ) δ: 0.82 (3H, d, J=6.7 Hz), 0.87 (6H, m), 0.90-1.12 (3H, m), 1.28 (3H, d, J=7.2 Hz), 1.37 (3H, d, J=6.2 Hz), 1.42-1.8.0 (6H, m), 2.06 (1H, m), 3.22 (3H, s), 3.34 (1H, dd, J 1 =6.9 Hz, J 2 =2.8 Hz), 3.46 (1H, m), 4.28 (1H, m), 4.37 (1H, dd, J 1 =9.7 Hz, J 2 =2.8 Hz), 5.09 (1H, m), 5.88, 6.01 (2H, ABq, J=5.9 Hz), 8.10 (1H, s), 8.54 (1H, s); MS (TSP): 624 (M + +H).

›Example 221

3,3,5,5-Tetramethylcyclohexyloxycarbonyloxy-methyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 2, 202 mg of the title compound was obtained from 158 mg of sodium (1S,5R,6s)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate and 200 mg of 3,3,5,5-tetramethylcyclohexyloxycarbonyloxymethyl iodide.

NMR (CDCl 3 ) δ: 0.94 (6H, s), 1.04′(6H, s), 1.10-1.23 (2H, m), 1.83 (4H, m), 3.22′(3H, s), 3.34 (1H, dd, J 1 =6.7 Hz, J 2 =2.8 Hz), 3.47 (1H, m), 4.28 (1H, m), 4.36 (1H, dd, J 1 =9.8 Hz, J 2 =2.8 Hz), 4.92 (1H, m), 5.91, 5.94 (2H, ABq, J=5.9′Hz), 8.10 (1H, s), 8.53 (1H, s); MS (TSP): 624 (M + +H).

›Example 222

2-Adamantyloxycarbonyloxymethyl (1S5R,6S)-6-((1R)-1-Hydroxyethyl)-2-(7-methanesulfonyl-imidazo[5,1 b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

In the same manner as in Example 2, 134 mg of the title compound was obtained from 109 mg of sodium (1S,5R,6s)-6-((1R-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate and 150mg of 2-adamantyloxycarbonyloxymethyl iodide. NMR (CDCl 3 ) δ: 1.28 (3H, d, J=7.1 Hz), 1.37 (3H, d, J=6.3 Hz), 1.52-2.12 (14H, m), 3.23 (3H, s), 3.35 (1H, dd, J 1 =6.6 Hz, J 2 =2.8 Hz), 3.46 (1H, m), 4.29 (1H, m), 4.37 (1H, dd J 1 =9.8 Hz, J 2 =2.8 Hz), 4.83, (1H, m), 5.92, 5.97 (2H, ABq, J 1 =5.8 Hz), 8.10 (1H, s), 8.53 (1H, s); MS (TSP): 620 (M + +H).

›Example 223

1-((Indan-2-yl)Oxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers).

In the same manner as in Example 2, 137 mg of the title compound was obtained from 180 mg of sodium (1S,5R,6s)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate and 250 mg of 1-((indan-2-yl)oxycarbonyloxy)ethyl iodide.

NMR (CDCl 3 ) δ: 1.28 (3H, m), 1.38 (3H, d, J=6.3 Hz), 1.57, 1.64 (total 3H, d each, J=5.5 Hz), 3.17-3.40 (5H, m), 3.23′(3H, s), 4.29 (1H, m), 4.36 (1H, m), 5.45 (1H, m), 5.51:′(1H, m), 6.95 (1H, m), 7.19 (4H, m), 8.08 (1H, s), 8.55 (1H, s); MS (TSP): 616 (M + +H).

›Example 224

1-(2-Methylphenoxycarbonyloxy)ethyl (1S,5R,65)-6-((1R)-1-Hydroxyethyl)-1-methyl-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers)

In the same manner as in Example 2, 214.0 mg of the title compound was obtained from 200.0 mg of sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate and 500 mg of 1-(2-methylphenoxycarbonyloxy)ethyl iodide.

NMR (CDCl 3 ) δ: 1.28, 1.30 (total 3H, d each, J=7.3 Hz), 1.38, 140 (total 3H, d each, J=6.3 Hz), 1.69, 1.74 (total 3H, d each, J=5.4 Hz), 1.80 (1H, m), 2.20, 2.28 (total 3H, s each), 3.21 (3H, s), 3.33 ′(1H, m), 3.46 (1H, m), 4.28 (1H, m), 4.35 (1H, m), 7.01 (1H, m), 7.23 (4H, m), 8.05, 8.06 (total 1H, s each), 8.53, 8.56 (total 1H, s each); MS (TSP): 590 (M + +H).

›Example 225

1-(2-Ethylphenoxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-1-methyl-2-7-methanesulfonylimidazo[5,1-b]thiazol -2-yl)-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers).

In the same manner as in Example 2, 149.0 mg of the title compound was obtained from 200.10 mg of sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methanesulfonylimidazo[5,1-b]thiazol 2-yl)-1-carbapen-2-em-3-carboxylate and 500 mg of 1-(2-ethyl phenoxycarbonyloxy)ethyl iodide.

NMR (CDCl 3 ) δ: 1.14, 1.21 (total 3H, t each, J=7.3 Hz), 1.28, 1.30 (total 3H, d each, J=7.3 Hz), 1.38, 1.40 (total 3H, d each, J=6.3 Hz), 1.69, 1.74 ( 1 total 3H, d each, J=5.4 Hz), 1.90 (1H, m), 2.56, 2.65 (total 2H, q each, J=7.3 Hz), 3.21 (3H, s), 3.33 (1H, m), 3.46 (1H, m), 4.28 (1H, m), 4.39 (1H, m), 701 (1H, m) 7.22 (4H, m), 8.05 (1H, s), 8.52, 8.55 (total 1H, s each); MS (TSP): 604 (M + +H).

›Example 226

(3-Methylphenoxycarbonyloxy)ethyl (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-1-methyl-2-(7methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate (a Mixture of Diastereomers).

In the same manner as in Example 2, 183.0 mg of the title compound was obtained from 200.0 mg of sodium (1S,5R,6S)-6-((1R)-1hydroxyethyl)-1-methyl-2-(7-methanesulfonylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate and 500 mg of 1-(3-methylphenoxycarbonyloxy)ethyl iodide.

NMR (CDCl 3 ) δ: 1.28, 1.30 (total 3H, d each, J=7.3 Hz), 1.38, 1.40 (total 3H, d each, J=6.3 Hz), 1.69, 1.74 (total 3H, d each, J=5.4 Hz), 1.95 (1H, d, J=4.6 Hz), 2.34, 2.36 (total 1H, s each), 3.21 (3H, s), 3.33 (1H, m), 3.46 (1H,

›Tables in the description — 2

EXAMPLE	R 1	R 2	R 3	R 4	R 5	R
1	CH 3	*	H	H	C(O)CH 2 CH 3	Na
2	CH 3	*	H	H	C(O)CH 2 CH 3
3	CH 3	*	H	H	CH═NOH	Na
					(Derived from low-polarity
					side chain component)
4	H	H	*	H	CH═NOCH 3	Na
					(Derived from low polarity
					side chain component)
5	H	H	*	H	CH═NOCH 3 (Derived from low-polarity side chain component)
6	CH 3	*	H	H	C(O)C(CH 3 ) 3	Na
7	CH 3	*	H	H	C(O)C(CH 3 ) 3
8	H	*	CH 3	H	C(O)CH 3	Na
9	H	*	CH 3	H	C(O)CH 3
10	CH 3	*	H	H	C(O)CH(CH 3 )NHCHO	Na
					(High polarity component)
11	CH 3	*	H	H	C(O)CH(CH 3 )NHCHO	Na
					(Low polarity component)
12	CH 3	*	H	H	C(O)CH(CH 3 ) 2	Na
13	CH 3	*	H	H	C(O)CH(CH 3 ) 2
14	H	H	*	H	C(O)CH 2 CH 3	Na
15	H	*	H	H	C(O)CH 3	Na
16	H	*	H	H	C(O)CH 3
17	H	*	H	H	C(O)CH(CH 3 ) 2	Na
18	H	*	H	H	C(O)CH(CH 3 ) 2
19	CH 3	*	H	CH 3	C(O)CH 3	Na
20	CH 3	*	H	CH 3	C(O)CH 3
21	CH 3	*	CH 3	H	C(O)CH 3	Na
22	CH 3	*	CH 3	H	C(O)CH 3
23	H	*	H	H	SO 2 CH 3	Na
24	H	H	*	H	SO 2 CH 3	Na
25	CH 3	H	*	H	SO 2 CH 3	Na
26	CH 3	*	H	H	S(O)CH 3	Na
27	H	*	H	H	C(O)CH 2 CH 3	Na
28	H	*	H	H	C(O)CH 2 CH 3
29	H	H	*	H	C(O)CH 3
30	CH 3	*	H	H	SO 2 CH 2 CH 3	Na
31	CH 3	*	H	H	SO 2 NHCH 3	Na
32	H	*	H	H	SO 2 NHCH 3	Na
33	H	*	H	CH 3	C(O)CH 3	Na
34	H	*	H	H	SO 2 CH 2 CH 3	Na
35	CH 3	*	H	H
Na
36	H	*	H	H	C(O)CH 2 OH	Na
37	CH 3	*	H	H	C(O)Ph	Na
38	H	H	*	H	C(O)CH 2 OH	Na
39	H	*	H	H	C(O)Ph	Na
40	CH 3	*	H	H
Na
41	CH 3	*	H	H	F	Na
42	CH 3	*	H	H	SO 2 N(CH 3 )CH 2 CH 2 OH	Na
43	CH 3	*	H	H	C(O)CH 2 NHC(O)CH 3	Na
44	CH 3	*	H	CH 3	SO 2 CH 3	Na
45	CH 3	*	H	CH 3	S(O)CH 3	Na
46	CH 3	*	H	H	C(O)CH 3
47	CH 3	*	H	H	C(O)CH 3
48	CH 3	*	H	H	C(O)CH 3
49	CH 3	*	H	H	C(O)CH 3
50	CH 3	*	H	H	C(O)CH 3
51	CH 3	*	H	H	C(O)CH 3
52	CH 3	*	H	H	C(O)CH 3
53	CH 3	*	H	H	CH 2 NHC(O)CH 3	Na
54	CH 3	*	H	H	CH 2 NHC(O)CH 3
55	CH 3	*	H	H	CH 2 NHC(O)CH 3
56	CH 3	*	H	H	CH 2 NHC(O)CH 3
57	CH 3	*	H	H	CH 2 NHC(O)CH 3
58	CH 3	*	H	H	CH 2 NHC(O)CH 3
59	CH 3	*	H	H	CH 2 NHC(O)CH 3
60	CH 3	*	H	H	CH 2 NHC(O)CH 3
61	CH 3	*	H	H	CH 2 NHC(O)CH 3
62	CH 3	*	H	H	SO 2 CH 3	Na
63	CH 3	*	H	H	SO 2 CH 3
64	CH 3	*	H	H	SO 2 CH 3
65	CH 3	*	H	H	SO 2 CH 3
66	CH 3	*	H	H	SO 2 CH 3
67	CH 3	*	H	H	SO 2 CH 3
68	CH 3	*	H	H	SO 2 CH 3
69	CH 3	*	H	H	SO 2 CH 3
70	CH 3	*	H	H	SO 2 CH 3
71	CH 3	*	H	H	C(O)CH 2 OH	Na
72	CH 3	*	H	H	C(O)CH 2 OH
73	CH 3	*	H	H	C(O)CH 2 OH
74	CH 3	*	H	H	C(O)CH 2 OH
75	CH 3	*	H	H	C(O)CH 2 OH
76	CH 3	*	H	H	C(O)CH 2 OH
77	CH 3	*	H	H	C(O)CH 2 OH
78	CH 3	*	H	H	C(O)CH 2 OH
79	CH 3	*	H	H	C(O)CH 2 OH
80	CH 3	*	H	H	C(O)CH 2 C(O)N(CH 3 ) 2	Na
81	CH 3	*	H	H	C(O)CH 2 C(O)N(CH 3 ) 2
82	CH 3	*	H	H	C(O)CH 2 C(O)N(CH 3 ) 2
83	CH 3	*	H	H	C(O)CH 2 C(O)N(CH 3 ) 2
84	CH 3	*	H	H	C(O)CH 2 C(O)N(CH 3 ) 2
85	CH 3	*	H	H	C(O)CH 2 C(O)N(CH 3 ) 2
86	CH 3	*	H	H	C(O)CH 2 C(O)N(CH 3 ) 2
87	CH 3	*	H	H	C(O)CH 2 C(O)N(CH 3 ) 2
88	CH 3	*	H	H	SO 2 N(CH 3 ) 2	Na
89	CH 3	*	H	H	SO 2 N(CH 3 ) 2
90	CH 3	*	H	H	SO 2 N(CH 3 ) 2
91	CH 3	*	H	H	SO 2 N(CH 3 ) 2
92	CH 3	*	H	H	SO 2 N(CH 3 ) 2
93	CH 3	*	H	H	SO 2 N(CH 3 ) 2
94	CH 3	*	H	H	SO 2 N(CH 3 ) 2
95	CH 3	*	H	H	SO 2 N(CH 3 ) 2
96	CH 3	*	H	H	CO 2 CH 3	Na
97	CH 3	*	H	H	SO 2 NCH 3 (OCH 3 )	Na
98	CH 3	*	H	H	C(O)CF 3	Na
99	CH 3	*	H	H	SO 2 NH 2	Na
100	CH 3	*	H	H
Na
101	CH 3	*	H	H
Na
102	CH 3	*	H	H
Na
103	CH 3	*	H	CH 3	C(O)CH 2 OH	Na
104	H	*	H	CH 3	SO 2 CH 3	Na
105	H	*	H	CH 3	S(O)CH 3	Na
106	H	*	H	CH 3	C(O)CH 2 OH	Na
107	CH 3	*	H	CH 3	SO 2 CH 3
108	CH 3	*	H	H	C(O)CH 2 NHSO 2 CH 3	Na
109	CH 3	*	H	CH 3	SCH 3	Na
110	CH 3	*	H	H	CH 2 NHSO 2 CH 3	Na
111	CH 3	*	H	H	SCH 3	Na
112	H	*	H	H	SO 2 N(CH 3 ) 2	Na
113	H	*	H	H	SO 2 NH 2	Na
114	CH 3	*	H	H	(E)-CH═CHC(O)CH 3	Na
115	CH 3	*	H	CH 3	CHO	Na
116	H	*	H	H	SCH 3	Na
117	H	*	H	H	S(O)CH 3	Na
118	H	*	H	H	C(O)CH 2 NHSO 2 N(CH 3 ) 2	Na
119	CH 3	*	H	H	C(O)CH 2 NHSO 2 N(CH 3 ) 2	Na
120	H	*	H	CH 3	SCH 3	Na
121	CH 3	*	H	H	C(O)CH 2 NH 2	Na
122	CH 3	*	H	H	CH 2 NH 2	Na
123	CH 3	*	H	H	C(O)CH 2 NHSO 2 CH 2 CH 2 NH 2	Na
124	H	*	H	H	C(O)CH 2 NHSO 2 CH 2 CH 2 NH 2	Na
125	CH 3	*	H	SO 2 CH 3	H	Na
126	CH 3	*	H	SCH 3	H	Na
127	CH 3	*	H	SCH 3	SCH 3	Na
128	CH 3	*	H	H	SPh	Na
129	H	H	*	H	SCH 3	Na
130	H	*	H	H	SPh	Na
131	CH 3	*	SCH 3	H	H	Na
132	CH 3	*	H	H	SCH 2 CH 3	Na
133	H	*	SCH 3	H	H	Na
134	H	*	H	H	SCH 2 CH 3	Na
135	H	*	CH 3	H	SCH 3	Na
136	CH 3	*	H	SCH 3	S(O)CH 3	Na
137	H	*	CH 2 OH	H	SCH 3	Na
138	H	*	Ph	H	H	Na
139	H	*	H	H	C(O)CH 2 NH 2	Na
140	CH 3	*	H	S(O)CH 3	H	Na
141	CH 3	*	H	S(O)CH 3	S(O)CH 3	Na
142	CH 3	*	H	S(O)CH 3	SO 2 CH 3	Na
143	CH 3	*	H	SO 2 CH 3	SO 2 CH 3	Na
144	H	*	CH 2 NH 2	H	H	Na
145	H	*	CH 2 OH	H	H	Na
146	H	*	H	SCH 3	SCH 3	Na
147	CH 3	*	H	C(O)CH 3	SCH 3	Na
148	CH 3	*	SCH 3	H	SCH 3	Na
149	CH 3	*	H	C(O)CH 3	SO 2 CH 3	Na
150	CH 3	*	H	Br	SCH 3	Na
151	H	*	H	C(O)CH 3	SCH 3	Na
152	CH 3	*	H	CN	SCH 3	Na
153	H	*	SCH 3	H	SCH 3	Na
154	CH 3	*	H	Cl	SCH 3	Na
155	H	*	H	CN	SCH 3	Na
156	CH 3	*	H	H	SCH 2 CH 2 CH 3	Na
157	H	*	H	H	SCH 2 CH 2 CH 3	Na
158	CH 3	*	H	H	SCH(CH 3 ) 2	Na
159	H	*	H	H	SCH(CH 3 ) 2	Na
160	CH 3	*	H	CH 3	SO 2 CH 3
161	CH 3	*	H	CH 3	SO 2 CH 3
162	CH 3	*	H	CH 3	SO 2 CH 3
163	CH 3	*	H	CH 3	SO 2 CH 3
164	CH 3	*	H	CH 3	SO 2 CH 3
165	CH 3	*	H	CH 3	SO 2 CH 3
166	CH 3	*	H	CH 3	C(O)CH 3
167	CH 3	*	H	CH 3	C(O)CH 3
168	CH 3	*	H	CH 3	C(O)CH 3
169	CH 3	*	H	CH 3	C(O)CH 3
170	CH 3	*	H	CH 3	C(O)CH 3
171	CH 3	*	H	CH 3	C(O)CH 3
172	CH 3	*	H	H	C(O)CH 3
173	CH 3	*	H	H	C(O)CH 3
174	CH 3	*	H	H	C(O)CH 3
175	CH 3	*	H	H	C(O)CH 3
176	CH 3	*	H	H	C(O)CH 3
177	CH 3	*	H	H	C(O)CH 3
178	CH 3	*	H	H	C(O)CH 3
179	CH 3	*	H	H	C(O)CH 3
180	CH 3	*	H	H	C(O)CH 3
181	CH 3	*	H	H	C(O)CH 3
182	CH 3	*	H	H	SO 2 CH 3
183	CH 3	*	H	H	SO 2 CH 3
184	CH 3	*	H	H	SO 2 CH 3
185	CH 3	*	H	H	SO 2 CH 3
186	CH 3	*	H	H	SO 2 CH 3
187	CH 3	*	H	H	SO 2 CH 3
188	CH 3	*	H	H	SO 2 CH 3
189	CH 3	*	H	H	SO 2 CH 3
190	CH 3	*	H	H	SO 2 CH 3
191	CH 3	*	H	H	SO 2 CH 3
192	CH 3	*	H	H	SO 2 CH 3
193	CH 3	*	H	H	SO 2 CH 3
194	CH 3	*	H	H	SO 2 CH 3
195	CH 3	*	H	H	SO 2 CH 3
196	CH 3	*	H	H	SO 2 CH 3
197	CH 3	*	H	H	SO 2 CH 3
198	CH 3	*	H	H	SO 2 CH 3
199	CH 3	*	H	H	SO 2 CH 3
200	CH 3	*	H	H	SO 2 CH 3
201	CH 3	*	H	H	SO 2 CH 3
202	CH 3	*	H	H	SO 2 CH 3
203	CH 3	*	H	H	SO 2 CH 3
204	CH 3	*	H	H	SO 2 CH 3
205	CH 3	*	H	H	SO 2 CH 3
206	CH 3	*	H	H	SO 2 CH 3
207	CH 3	*	H	H	SO 2 CH 3
208	CH 3	*	H	H	SO 2 CH 3
209	CH 3	*	H	H	SO 2 CH 3
210	CH 3	*	H	H	SO 2 CH 3
211	CH 3	*	H	H	SO 2 CH 3
212	CH 3	*	H	H	SO 2 CH 3
213	CH 3	*	H	H	SO 2 CH 3
214	CH 3	*	H	H	SO 2 CH 3
215	CH 3	*	H	H	SO 2 CH 3
216	CH 3	*	H	H	SO 2 CH 3
217	CH 3	*	H	H	SO 2 CH 3
218	CH 3	*	H	H	SO 2 CH 3
219	CH 3	*	H	H	SO 2 CH 3
220	CH 3	*	H	H	SO 2 CH 3
221	CH 3	*	H	H	SO 2 CH 3
222	CH 3	*	H	H	SO 2 CH 3
223	CH 3	*	H	H	SO 2 CH 3
224	CH 3	*	H	H	SO 2 CH 3
225	CH 3	*	H	H	SO 2 CH 3
226	CH 3	*	H	H	SO 2 CH 3
227	CH 3	*	H	H	SO 2 CH 3
228	CH 3	*	H	H	SO 2 CH 3
229	CH 3	*	H	H	SO 2 CH 3
230	CH 3	*	H	H	SO 2 CH 3
231	CH 3	*	H	H	SO 2 CH 3
232	CH 3	*	H	H	SO 2 CH 3
233	CH 3	*	H	H	SO 2 CH 3
234	CH 3	*	H	H	SO 2 CH 3
235	CH 3	*	H	H	SO 2 CH 3
236	CH 3	*	H	H	SO 2 CH 3	CH 2 CH 3
237	CH 3	*	H	H	SO 2 CH 3	CH(CH 3 ) 2
238	CH 3	*	H	H	SO 2 CH 3	(CH 2 ) 3 CH 3
239	CH	*	H	H	SO 2 CH 3
240	CH	*	H	H	SCH 3
241	CH 3	*	H	H	SCH 3
242	CH 3	*	H	H	SCH 3
243	CH 3	*	H	H	SCH 3
244	CH 3	*	H	H	SCH 3
245	CH 3	*	H	H	SCH 3
246	CH 3	*	H	H	SCH 3
247	CH 3	*	H	H	SCH 3
248	CH 3	*	H	H	SCH 3
249	CH 3	*	H	H	SCH 3
250	CH 3	*	H	H	SCH 3
251	CH 3	*	H	H	SCH 3
252	CH 3	*	H	H	SCH 3
253	CH 3	*	H	H	SCH 3
254	CH 3	*	H	H	SCH 3
255	CH 3	*	H	H	SCH 3
256	CH 3	*	H	H	SCH 3
257	CH 3	*	H	H	SCH 3
258	CH 3	*	H	H	SCH 3
259	CH 3	*	H	H	SCH 3
260	CH 3	*	H	H	SCH 3
261	CH 3	*	H	H	SCH 3
262	CH 3	*	H	H	SCH 3
263	CH 3	*	H	H	SCH 3
264	CH 3	*	H	H	SCH 3
265	CH 3	*	H	H	SCH 3
266	CH 3	*	H	H	SCH 3
267	CH 3	*	H	H	SCH 3
268	CH 3	*	H	H	SCH 3
269	CH 3	*	H	H	SCH 3
270	CH 3	*	H	H	SCH 3
271	CH 3	*	H	H	SCH 3
272	CH 3	*	H	H	SCH 3
273	CH 3	*	H	H	SCH 3
274	CH 3	*	H	H	SCH 3
275	CH 3	*	H	H	SCH 3
276	CH 3	*	H	H	SCH 3
277	CH 3	*	H	H	SCH 3
278	CH 3	*	H	H	SCH 3
279	CH 3	*	H	H	SCH 3
280	CH 3	*	H	H	SCH 3
281	CH 3	*	H	H	SCH 3
282	CH 3	*	H	H	SCH 3
283	CH 3	*	H	H	SCH 3
284	CH 3	*	H	H	SCH 3
285	CH 3	*	H	H	SCH 3
286	CH 3	*	H	H	SCH 3
287	CH 3	*	H	H	SCH 3
288	CH 3	*	H	H	SCH 3
289	CH 3	*	H	H	SCH 3
290	CH 3	*	H	H	SCH 3
291	CH 3	*	H	H	SCH 3
292	CH 3	*	H	H	SCH 3
293	CH 3	*	H	H	SCH 3
294	CH 3	*	H	H	SCH 3
295	CH 3	*	H	H	SCH 3
296	CH 3	*	H	H	SCH 3
297	CH 3	*	H	H	SCH 3
298	CH 3	*	H	H	SCH 3
299	CH 3	*	H	H	SCH 3
300	CH 3	*	H	H	SCH 3
301	CH 3	*	H	H	SCH 3
302	CH 3	*	H	H	SCH 3
303	CH 3	*	H	H	SCH 3
304	CH 3	*	H	H	SCH 3
305	CH 3	*	H	H	SCH 3
306	CH 3	*	H	H	SCH 3
307	CH 3	*	H	H	SCH 3	(CH 2 ) 6 CH 3
308	CH 3	*	H	H	SCH 3
309	CH 3	*	H	H	SCH 3
310	CH 3	*	H	H	SCH 3
311	CH 3	*	H	H	SCH 3
312	CH 3	*	H	H	SCH 3
313	CH 3	*	H	H	SCH 3
314	CH 3	*	H	H	SCH 3
315	CH 3	*	H	H	SCH 3
316	CH 3	*	H	H	SCH 3
317	CH 3	*	H	H	SCH 3
318	CH 3	*	H	H	SCH 3
319	CH 3	*	H	H	SCH 3
320	CH 3	*	H	H	SCH 3
321	CH 3	*	H	H	SCH 3
322	CH 3	*	H	H	SO 2 N(CH 3 ) 2
323	CH 3	*	H	H	SCH 3
324	CH 3	*	H	H	SCH 3
325	CH 3	*	H	H	SCH 3
326	CH 3	*	H	H	C(O)CH 3
327	CH 3	*	H	H	SO 2 N(CH 3 ) 2
328	CH 3	*	H	H	S(O)CH 3
329	CH 3	*	H	H	SCH 3
330	CH 3	*	H	H	SCH 3
331	CH 3	*	H	H	SCH 3
332	CH 3	*	H	H	SCH 3

nt: not tested Compound A: imipenem; Compound C: meropenem.

	Example	Example	Example
DHP-I	19	26	27	Example 44	Example 62
Porcine	77	44	38	100	64
Mouse	45	11	1.2	nt	1.5
DHP-I	Example 71	Example 88	Compound A	Compound C
Porcine	33	73	<0.3	41
Mouse	<0.1	<0.1	14	8.5
In the table,

description truncated at 500,000 characters. 1 of 264 part labels are ours — the grant heads the rest

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Claims as granted

24 claims

Classifications

6 codes

IPC · International Patent Classification

Section A — Human necessities

A61P31/04

Section C — Chemistry; metallurgy

C07D519/06
C07D477/14
C07D519/00

USPC · US Patent Classification

514/210.9540/302

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Responses

1 RCE

Examiner

Mark L. Berch

art unit 1624 · TC 1600

Law firm

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Citations: 11 back · 2 forward

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Documents

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Chain of title

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